Implantable medical systems, devices, and methods for affecting cardiac function through diaphragm stimulation, and for monitoring diaphragmatic health

ABSTRACT

Devices, systems and methods provide forms of asymptomatic diaphragmatic stimulation (ADS) therapy that affect pressures within the intrathoracic cavity, including: 1) dual-pulse ADS therapy, during which a first ADS pulse is delivered during a diastolic phase of a cardiac cycle and a second ADS pulse is delivered during a systolic phase, 2) paired-pulse ADS therapy, during which a first ADS pulse is delivered, closely followed by a second ADS pulse, with the second ADS pulse functioning to extend or enhance a phase of a transient, partial contraction of the diaphragm, and 3) multiple-pulse ADS therapy, during which a stream of ADS pulses is delivered, wherein the time between pulses is based on heart rate. Devices, systems and methods also monitor electromyography (EMG) activity of the diaphragm relative to baseline activity to assess the health of a diaphragm subject to ADS therapy and to adjust ADS therapy parameters or sensing parameters.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application claims the benefit of and priority to U.S. ProvisionalPatent Application Ser. No. 62/906,682, filed Sep. 26, 2019, for“Implantable Medical Systems, Devices and Methods that Affect PressuresWithin the Intrathoracic Cavity,” the entire disclosure of which isincorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates generally to systems, devices and methodfor affecting cardiac function, and more particularly, to implantablemedical systems, devices and methods that affect pressures within theintrathoracic cavity through diaphragm stimulation. The presentdisclosure also relates generally to systems, devices and method formonitoring patient health, and more particularly, to implantable medicalsystems, devices and methods that monitor electromyography (EMG)electrical activity of the diaphragm to assess patient health.

BACKGROUND

The diaphragm is a dome shaped skeletal muscle structure separating thethoracic and abdominal cavities. It is the major muscular organresponsible for mechanical respiratory motion by deflecting downwardsupon contraction during inspiration. The phrenic nerve innervates thediaphragm and acts as the primary method of nervous excitation to signalcontraction. The external and internal intercostal muscles also elevatethe ribs increasing the anterior-posterior diameter of the thoraciccavity. During inspiration, the movement of the diaphragm results inexpansion and negative pressure within the thoracic cavity as thediaphragm and intercostal muscles increase the size of the thorax. Theexpanding thorax causes the intrathoracic pressure to decrease belowatmospheric pressure and air moves into the lungs. During exhalation,the inspiratory muscles relax, and the elastic recoil of the lungtissues, combined with a rise in intrathoracic pressure, causes air tomove out of the lungs.

Changes in intrathoracic pressure from diaphragmatic contraction andthoracic expansion may be transmitted to the intrathoracic structuresnamely the heart, pericardium, great arteries and veins. Spontaneousinspiration produces a negative pleural pressure affectingcardiovascular performance including atrial filling (preload) andresistance to ventricular emptying (afterload). This affect can beobserved in cardiovascular hemodynamic parameters during normal functionwhen diaphragmatic contractions are of sufficient duration, intensityand expansiveness to cause inspiration, and used in clinical practiceduring Vasalva and Mueller maneuvers where patients forcefully inspireor expire using diaphragmatic muscles against a closed glottis causing arapid change in thoracic pressures. These maneuvers result in pronouncedrapid acute changes to intrathoracic pressure, which changes in turnalter pressure gradients associated with the cardiac chambers andvessels to affect cardiac functions, including cardiac filling andoutput.

The effects of intrathoracic pressure on cardiac systemic performanceare complex. Hiccups, which result from rapid partial diaphragmaticcontractions causing rapid decreases to intrathoracic pressure, havebeen previously used to characterize their effects of cardiac andsystemic performance. Studies of both animal and human subjectsdemonstrated changes to hemodynamic parameters including overallventricular diastolic and systolic pressures, cardiac output and changesto systemic measures including aortic distention and vascularresistance. These studies also demonstrated that rapid intrathoracicpressure effect changes are extremely sensitive to timing relative tothe cardiac cycle, with different observed if the hiccups occur duringventricular diastolic, systole, or during the diastole-systoletransition.

BRIEF DESCRIPTION OF THE DRAWINGS

Various aspects of systems, devices and methods that affect pressureswithin the intrathoracic cavity through diaphragmatic stimulation willnow be presented in the detailed description by way of example, and notby way of limitation, referring to the accompanying drawings, wherein:

FIG. 1 is an illustration of an asymptomatic diaphragm stimulation (ADS)therapy delivery mechanism shown in two alternate locations relative tothe thoracic cavity of a patient.

FIG. 2A is an illustration of the thoracic cavity at end inspiration.

FIG. 2B is an illustration of the thoracic cavity at end expiration.

FIG. 2C is an illustration of a diaphragm and sacrum viewed from theinferior side of the diaphragm and in the caudal direction.

FIG. 3A is an illustration of a multi-piece embodiment of an implantablemedical device for providing ADS therapy implanted on the inferior sideof the diaphragm.

FIG. 3B is an illustration of the implantable medical device of FIG. 3A.

FIG. 4A is an illustration of a single-piece embodiment of animplantable medical device for providing ADS therapy implanted on theinferior side of the diaphragm.

FIG. 4B is an illustration of the implantable medical device of FIG. 4A.

FIG. 5A is an illustration of an implantable medical device thatprovides ADS therapy and another therapy, such as cardiac rhythmmanagement (CRM) therapy.

FIG. 5B is an illustration of the implantable medical device of FIG. 5A.

FIG. 6 is a block diagram of a medical system that includes an externaldevice and one or more implantable devices that provide ADS therapyoperating in a master/slave arrangement.

FIG. 7 is a block diagram of an implantable medical device configured toaffect pressures within the intrathoracic cavity through delivery ofdiaphragmatic stimulation by an ADS therapy delivery mechanism.

FIG. 8A is a schematic diagram of an ADS therapy including dualstimulation pulses per cardiac cycle, with one pulse delivered duringlate diastole and the other pulse delivered during early systole.

FIG. 8B are illustrations of an electrocardiogram (ECG) waveform and adiaphragmatic acceleration waveform including spaced apart pairs oftransient, partial contractions of the diaphragm resulting from deliveryof the ADS therapy of FIG. 8A, wherein each transient, partialcontraction results from the delivery of a single ADS pulse and includesa caudal phase, during which a portion of the diaphragm is moving in thecaudal direction, and cranial phase during which a portion of thediaphragm is moving in the cranial direction.

FIG. 9 is a flowchart of a method of affecting pressure in anintrathoracic cavity of a patient through the delivery of dual ADSpulses per cardiac cycle.

FIG. 10 are illustrations of an ECG waveform and a diaphragmaticacceleration waveform including a series of transient, partialcontractions, each having a caudal phase followed by an extended orenhance cranial phase that results from delivery of a closely timed pairof ADS pulses.

FIG. 11 is a flowchart of a method of affecting pressure in anintrathoracic cavity of a patient through delivery of paired ADS pulses.

FIGS. 12A and 12B are illustrations of an ECG waveform and adiaphragmatic acceleration waveform including a series of transient,partial contractions of the diaphragm resulting from different ADStherapies, including a therapy based on FIG. 8A wherein a dual ADSpulses are delivered each cardiac cycle (FIG. 12A) and a therapy whereina greater number of ADS pulses are delivered each cardiac cycle based onheart rate (FIG. 12B).

FIG. 13 is a flowchart of a method of affecting pressure in anintrathoracic cavity of a patient through delivery of multiple ADSpulses per cardiac cycle.

FIG. 14A is an illustration of a composite ECG/electromyography (EMG)signal corresponding to a baseline ECG/EMG signal for a patient.

FIG. 14B is an illustration of a composite ECG/EMG signal correspondingto an ECG/EMG signal of a patient at a time after activation of ADStherapy.

FIGS. 15A, 15B, and 15C are illustrations of pure EMG signals withoutany ECG component, showing an EMG signal from a healthy patient (FIG.15A), from a patient with neuropathy (FIG. 15B), and from a patient withmyopathy (FIG. 15C).

FIGS. 16A, 16B and 16C are illustrations of composite ECG/EMG signalsobtained through different signal filter settings, including a firstwideband filter (FIG. 16A), a second wideband filter (FIG. 16B), and anarrowband filter (FIG. 16C).

FIG. 17 is a flowchart of a method of modifying sensing and/orstimulation parameters for an apparatus that affects pressure in anintrathoracic cavity of a patient through delivery of ADS therapy.

FIG. 18 is a flowchart of a method of monitoring patient health based onEMG electrical activity of the diaphragm.

SUMMARY

Devices, systems, and methods disclosed herein provide various forms ofasymptomatic diaphragmatic stimulation (ADS) therapy that affectpressures within the intrathoracic cavity to improve cardiac function.These forms of ADS therapy include: 1) dual-pulse ADS therapy, duringwhich a first ADS pulse is delivered during a diastolic phase of acardiac cycle and a second ADS pulse is delivered during a systolicphase, 2) paired-pulse ADS therapy, during which a first ADS pulse isdelivered, closely followed by a second ADS pulse, with the second ADSpulse functioning to extend or enhance a phase of a transient, partialcontraction of the diaphragm, and 3) multiple-pulse ADS therapy, duringwhich a stream of ADS pulses is delivered, wherein the time betweenpulses is based on heart rate.

In one aspect of the disclosure, an apparatus for providing dual-pulseADS therapy to affect pressure in an intrathoracic cavity of a patientincludes one or more electrodes configured for placement on or near adiaphragm, and a controller coupled to the one or more electrodes. Thecontroller is configured to deliver a diastolic stimulation pulse to thediaphragm of the patient during a diastolic phase of a cardiac cycle ofthe patient, and to deliver a systolic stimulation pulse to thediaphragm during a systolic phase of the cardiac cycle. The pulses aredelivered such that each of the diastolic stimulation pulse and thesystolic stimulation pulse results in an asymptomatic, transient,partial contraction of the diaphragm. To this end, respective pulsedelivery may be defined by stimulation parameters, including an offsetperiod or delay period, that time the delivery of the respective pulsesto produce separate asymptomatic, transient, partial contractions of thediaphragm.

In one aspect of the disclosure, a method of providing dual-pulse ADStherapy to affect pressure in an intrathoracic cavity of a patientincludes delivering a diastolic stimulation pulse to a diaphragm of thepatient during a diastolic phase of a cardiac cycle of the patient, anddelivering a systolic stimulation pulse to the diaphragm during asystolic phase of the cardiac cycle. The pulses are delivered such thateach of the diastolic stimulation pulse and the systolic stimulationpulse results in an asymptomatic, transient, partial contraction of thediaphragm. To this end, respective pulse delivery may be defined bystimulation parameters, including an offset period or delay period, thattime the delivery of the respective pulses to produce separateasymptomatic, transient, partial contractions of the diaphragm.

In one aspect of the disclosure, an apparatus for providing paired-pulseADS therapy to affect pressure in an intrathoracic cavity of a patientincludes one or more electrodes configured for placement on or near adiaphragm, and a controller coupled to the one or more electrodes. Thecontroller is configured to deliver a first stimulation pulse to thediaphragm of the patient, and to deliver a second stimulation pulse tothe diaphragm while the diaphragm is still in motion or contracting fromthe first stimulation pulse. The first stimulation pulse is configuredto induce a transient, partial contraction of the diaphragm comprising acaudal phase corresponding to a time during which a portion of thediaphragm is moving in a caudal direction, followed by a cranial phasecorresponding to a time during which the portion of the diaphragm ismoving in a cranial direction. The second stimulation pulse isconfigured to extend a duration of one of the caudal phase or thecranial phase. To this end, the second stimulation pulse may be definedby stimulation parameters, including an offset period or delay period,that time the delivery of the second pulse to extend the duration of oneof the caudal phase or the cranial phase.

In one aspect of the disclosure, a method of providing paired-pulse ADStherapy to affect pressure in an intrathoracic cavity of a patientincludes delivering a first stimulation pulse to a diaphragm of thepatient, and delivering a second stimulation pulse to the diaphragmwhile the diaphragm is still in motion or contracting from the firststimulation pulse. The first stimulation pulse induces a transient,partial contraction of the diaphragm comprising a caudal phasecorresponding to a time during which a portion of the diaphragm ismoving in a caudal direction, followed by a cranial phase correspondingto a time during which the portion of the diaphragm is moving in acranial direction. The second stimulation pulse extends a duration ofone of the caudal phase or the cranial phase. To this end, the secondstimulation pulse may be defined by stimulation parameters, including anoffset period or delay period, that time the delivery of the secondpulse to extend the duration of one of the caudal phase or the cranialphase.

In one aspect of the disclosure, an apparatus for providingmultiple-pulse ADS therapy to affect pressure in an intrathoracic cavityof a patient includes one or more electrodes configured for placement onor near a diaphragm, and a controller coupled to the one or moreelectrodes. The controller is configured to deliver a plurality ofstimulation pulses to the diaphragm of the patient during a cardiaccycle of the patient. Each of the plurality of stimulation pulsesresults in a corresponding transient, partial contraction of thediaphragm comprising a caudal phase corresponding to a time during whicha portion of the diaphragm is moving in a caudal direction, followed bya cranial phase corresponding to a time during which the portion of thediaphragm is moving in a cranial direction. To this end, the timingbetween successive stimulation pulses is based on heart rate and theduration of transient, partial contractions of the diaphragm, wherebythe timing between pulses allows for each pulse to produce a completeand separate transient, partial contraction of the diaphragm.

In one aspect of the disclosure, a method of providing multiple-pulseADS therapy to affect pressure in an intrathoracic cavity of a patientincludes delivering a plurality of stimulation pulses to a diaphragm ofthe patient during a cardiac cycle of the patient, wherein each of theplurality of stimulation pulses results in a corresponding transient,partial contraction of the diaphragm comprising a caudal phasecorresponding to a time during which a portion of the diaphragm ismoving in a caudal direction, followed by a cranial phase correspondingto a time during which the portion of the diaphragm is moving in acranial direction. To this end, the timing between successivestimulation pulses is based on heart rate and the duration of transient,partial contractions of the diaphragm, whereby the timing betweensuccessive stimulation pulses allows for each pulse to produce acomplete and separate transient, partial contraction of the diaphragm.

Devices, systems and methods disclosed herein also monitorelectromyography (EMG) activity of the diaphragm relative to baselineEMG activity to assess the health of a diaphragm subject to ADS therapyand to adjust ADS therapy parameters or sensing parameters.

In one aspect of the disclosure, an apparatus for affecting pressure inan intrathoracic cavity of a patient through delivery of ADS includesone or more electrodes configured for placement on or near a diaphragm,and a controller coupled to the one or more electrodes. The controlleris configured to deliver ADS therapy to the patient over a period oftime, where the ADS therapy comprises ADS pulses defined by a one ormore stimulation parameters. The controller is also configured toperiodically sense over the period of time, EMG electrical activityproduced by one or more skeletal muscles of the diaphragm in accordancewith one or more sensing parameters, and to determine if the EMGelectrical activity satisfies a criterion relative to baseline EMGelectrical activity of the patient that is sensed prior to ADS therapyactivation. The controller is further configured to adjust at least oneof the one or more stimulation parameters and the one or more sensingparameters if the criterion is not satisfied for purposes of improvingADS therapy.

In one aspect of the disclosure, a method of modifying sensing and/orstimulation parameters for an apparatus that affects pressure in anintrathoracic cavity of a patient through delivery of ADS therapyincludes delivering ADS therapy to the patient over a period of time.The ADS therapy comprises ADS pulses defined by a one or morestimulation parameters. The method also includes periodically sensingover the period of time, EMG electrical activity produced by one or moreskeletal muscles of a diaphragm in accordance with one or more sensingparameters, and determining if the sensed EMG electrical activitysatisfies a criterion relative to baseline EMG electrical activity ofthe patient that is sensed prior to ADS therapy activation. The methodfurther includes adjusting at least one of the one or more stimulationparameters and the one or more sensing parameters if the criterion isnot satisfied in order to improve ADS therapy.

In one aspect of the disclosure, an apparatus for monitoring the healthof a patient includes one or more electrodes configured for placement onor near a diaphragm, and a controller coupled to the one or moreelectrodes. The controller is configured to periodically sense over aperiod of time, EMG electrical activity produced by one or more skeletalmuscles of the diaphragm in accordance with one or more sensingparameters, and determine if the sensed EMG electrical activitysatisfies a criterion relative to baseline EMG electrical activity ofthe patient.

In one aspect of the disclosure, a method of monitoring the health of apatient includes periodically sensing over a period of time, EMGelectrical activity produced by one or more skeletal muscles of adiaphragm in accordance with one or more sensing parameters. The methodalso includes determining if the sensed EMG electrical activitysatisfies a criterion relative to baseline EMG electrical activity ofthe patient.

It is understood that other aspects of apparatuses and methods willbecome readily apparent to those skilled in the art from the followingdetailed description, wherein various aspects of apparatuses and methodsare shown and described by way of illustration. As will be realized,these aspects may be implemented in other and different forms and itsseveral details are capable of modification in various other respects.Accordingly, the drawings and detailed description are to be regarded asillustrative in nature and not as restrictive.

DETAILED DESCRIPTION

Disclosed herein are implantable medical devices, systems and methodsthat provide various forms of asymptomatic diaphragmatic stimulation(ADS) therapy that affects pressures within the intrathoracic cavity. Inone form of ADS therapy, referred to herein as dual-pulse ADS therapy, afirst ADS pulse is delivered during a diastolic phase of a cardiac cycleand a second ADS pulse is delivered during a systolic phase. In anotherform of ADS therapy, referred to herein as paired-pulse ADS therapy, afirst ADS pulse is delivered, closely followed by a second ADS pulse,with the second ADS pulse functioning to extend or enhance a transient,partial contraction of the diaphragm in a particular direction. Inanother form of ADS therapy, referred to herein as multiple-pulse ADStherapy, a continuous stream of ADS pulses are delivered, wherein thetime between pulses is based on heart rate.

Also disclosed are implantable medical devices, systems and methods thatassess the health of a diaphragm that is subject to ADS therapy and theheart failure status of a patient that is subject to ADS therapy. Thesesystems, devices, and methods monitor electromyography (EMG) activity ofthe diaphragm relative to baseline activity to determine patient statusand to adjust ADS therapy parameters, including stimulation parametersand/or sensing parameters.

Electrical stimulation to the diaphragm induces transient, partial,asymptomatic diaphragmatic contractions, which in turn induces changesin intrathoracic pressures. Appropriately timed and configureddiaphragmatic stimulation may improve cardiovascular performance andcardiac function, to thereby manage heart failure. For example,diaphragmatic stimulation synchronized with, or otherwise timed to anoccurrence of a cyclic cardiac event, such as ventricular systole mayaccelerate negative intrathoracic cavity pressure (suction) during leftventricular filling to increase filling volume, and then acceleratepositive intrathoracic cavity pressure (compression) to augment systoliccontractile forces generated by the left ventricle.

Because the management of heart failure is complex and physicians needto optimize numerous various and interdependent physiologic effectsbetween the heart and vessels, an objective of the therapy disclosedherein is to utilize evoked diaphragmatic contractions to optimize theoperating intrathoracic pressure conditions on the heart and vessels forimproving the patient's overall condition. These include: the bloodvolume to one or more chambers of the cardiovascular system within thethoracic cavity, end diastolic pressure (preload) that causes changes tosystolic output (starling), that mediates intracardiac blood flow(diastolic coronary perfusion) and operating mechanics (efficiency), orfor decreasing the compliance of the vessels responsible for cardiacfilling (vena cava and right atrium) or for altering the compliance ofcardiac vessels to better match the operational ability of the heart(impedance matching or optimization). These indirect physiologicmechanisms will augment the direct physiologic mechanism of mechanicallyaugmenting the mechanical forces of the heart and decreasing thevascular resistance to cardiac output.

Asymptomatic Diaphragmatic Stimulation

FIG. 1 is a schematic illustration of an asymptomatic diaphragmaticstimulation (ADS) therapy delivery mechanism 100 implanted in the regionof a patient's thoracic cavity 102 on or near the patient's diaphragm104. The ADS therapy delivery mechanism 100 is configured to deliverstimulation pulses to the diaphragm 104 in accordance with a diaphragmstimulation program. The ADS therapy delivery mechanism 100 may be oneor more electrodes configured to be positioned on or near a diaphragm.Although illustrated in FIG. 1 generically, the ADS therapy deliverymechanism 100 may be:

1) A standalone implantable medical device (IMD) in the form of either:a) a single-piece, unitary structure having no removable component partsand that houses electronics and carries the ADS therapy deliverymechanism, or b) a multi-piece IMD having a can that houses electronicsand a sub-structure, e.g., a lead, that carries the ADS therapy deliverymechanism. The sub-structure may be a lead that electrically andmechanically couples to the can, or may be a separate, unconnectedmodule that wirelessly communicates with the can.

2) Alternatively, the ADS therapy delivery mechanism 100 may be a partof an IMD that provides other therapy, such as cardiac rhythm management(CRM) device in the form of a pacemaker, cardiac resynchronizationtherapy device, or defibrillator. The part may be, for example, a lead,that carries the ADS therapy delivery mechanism and electrically andmechanically couples to the can of the CRM device, or may be a separate,unconnected module that wirelessly communicates with the can of the CRMdevice.

3) Or the ADS therapy delivery mechanism 100 may be a part of a medicalsystem that includes one or more implantable devices operating in amaster/slave arrangement together with an external device.

Continuing with FIG. 1 , the ADS therapy delivery mechanism 100 may beplaced, through conventional laparoscopy, at a selected surface regionof the diaphragm 104 on the inferior side of the diaphragm at a locationreferred to as an inferior implant location 120. Alternatively, the ADStherapy delivery mechanism 100 may be placed, through conventionalthoracotomy, at a selected surface region of the diaphragm 104 on thesuperior side of diaphragm 104 at a location referred to as a superiorimplant location 122. For example, the ADS therapy delivery mechanism100 may be positioned between the superior surface of diaphragm 104 andthe underside of the patient's left lung 124 a.

The thoracic cavity 102, also referred to as the intrathoracic cavityand the mediastinum, is a hermetically sealed cavity formed by variousconnected structures. These structures include the diaphragm 104, thethoracic sidewalls 106 a, 106 b, and layered walls 108, 110, near thetrachea 112 and the heart 114.

The diaphragm 104 is a dome-shaped skeletal muscle structure locatedbelow the lungs 124 a, 124 b that separates the thoracic cavity 102 fromthe abdominal cavity 126. The diaphragm 104 defines the lower end of thethoracic cavity 102 and is the major muscular organ responsible formechanical respiratory motion. The thoracic sidewalls 106 a, 106 b areformed of ribs 116 and membrane 118 filing the space between the ribs,and define the thoracic sidewalls 106 a, 106 b of the thoracic cavity102. The layered walls 108, 110 are formed of various membranes andvessels which lay over each other to form a seal at the top of thethoracic cavity 102.

Mechanical respiratory motion includes an inspiration or inhalationphase and an expiration or exhalation phase. As previously mentioned,the diaphragm 104 is the major muscular organ responsible for mechanicalrespiratory motion. The phrenic nerve (not shown) innervates thediaphragm 104 and sends signals to the diaphragm to control inspirationand expiration. These signals act as the primary mechanism forinitiating contraction of the diaphragm through nervous excitation.Since nervous endings responsible for pain sensation are absent withinthe diaphragm, a confine of therapy outputs are those which provide thedesired hemodynamic effects to the cardiovascular system whilesimultaneously minimizing the likelihood of field stimulation of painnerves contained within other nearby innervated thoracic cavitymusculature.

FIG. 2A is an illustration of the thoracic cavity at end inspiration.During inspiration, the diaphragm 104 contracts, e.g., flattens out, anddeflects downward, in a direction away from the lungs 124 a, 124 b.Concurrent with downward deflection of the diaphragm during inspiration,the external and internal intercostal muscles around the lungs 124 a,124 b elevate the ribs 116, thereby increasing the anterior-posteriordiameter of the thoracic cavity 102. During inspiration, the movement ofthe diaphragm 104 results in expansion and negative pressure within thethoracic cavity 102 as the diaphragm and intercostal muscles increasethe size of the thorax. The expanding thorax causes the pressure withinthe open space of thoracic cavity 102, i.e., the intrathoracic pressure,to decrease below atmospheric pressure. The pressure decrease causesexternal air to move into the lungs 124 a, 124 b.

FIG. 2B is an illustration of the thoracic cavity at end expiration.During expiration, the diaphragm 104 expands, e.g., assumes a domeshape, and deflects upward, in the direction of the lungs 124 a, 124 b.During expiration, the diaphragm 104, together with the external andinternal intercostal muscles around the lungs 124 a, 124 b relax. Thediaphragm 104 expands, e.g., resumes a dome shape, and the ribs 116de-elevate, thereby reducing the anterior-posterior diameter of thethoracic cavity 102, and causing the intrathoracic pressure to increaseabove atmospheric pressure. The increase in intrathoracic pressure incombination with the elastic recoil of lung tissues, causes air to moveout of the lungs.

Changes in the pressure within the open space of the thoracic cavity102, i.e., the intrathoracic pressure, due to diaphragm contraction andthoracic cavity expansion, and diaphragm expansion and thoracic cavitycontraction bring about changes in other pressures within theintrathoracic cavity, including pressures associated with intrathoracicstructures like the heart 114, pericardium, great arteries and veins.For example, changes in cardiovascular pressures, such as right atrial(RA) pressure, right ventricular (RV) pressure, left ventricular (LV)pressure, and aortic (AO) pressure result from changes in intrathoracicpressure.

In accordance with presently disclosed embodiments, intrathoracicpressure is manipulated through controlled delivery of diaphragmaticstimulation through an ADS therapy delivery mechanism, to bring aboutdesirable changes in other pressures within the intrathoracic cavity toimprove cardiac function. Through delivery of appropriately timedstimulation therapy to the diaphragm, transient, asymptomatic, partialcontractions of the diaphragm are induced in synchrony or near synchronywith one or more cardiac events to delivery ADS therapy are specifiedportions of a cardiac cycle. Timing the occurrences of these transient,asymptomatic, partial contractions relative to cardiac events results inchanges in intrathoracic pressure, which in turn, increases and/ordecreases pressures associated with the heart, pericardium, greatarteries and veins to thereby improve hemodynamic function of the heart.

As used herein, a “transient” contraction of the diaphragm is a short,twitching, caudal followed by cranial motion of the diaphragm that lastsin range of 60 to 180 msec., and is typically about 100 msec. A“partial” contraction of the diaphragm is the part or region of thediaphragm (less than the entirety of the diaphragm) that exhibits a“transient” contraction. For example, with reference to FIG. 2C, adiaphragm stimulation pulse delivered through an ADS therapy deliverymechanism 100 placed on the left hemisphere of a diaphragm 204 willresult in contraction of a portion 202 or part of the left hemispherethat is less than the entirety of the left hemisphere.

Signals indicative of pressures within the intrathoracic cavity,including intrathoracic pressure itself, and other pressures, such ascardiovascular pressures, may be monitored and used as a feedbackmechanism to adjust ADS therapy. To this end, one or more parametersthat define ADS therapy may be changed to obtain a desired increaseand/or decrease in pressures associated with the heart, pericardium,great arteries and veins. For example, in the case of electricalstimulation therapy, one or more of the timing at which an electricalstimulation pulse is delivered, a pulse waveform type, a pulseamplitude, a pulse duration, and a pulse polarity, may be adjusted orchanged.

Other signals indicative of pressures within the intrathoracic cavity,such as heart sounds, may also be monitored and used as a feedbackmechanism to adjust ADS therapy. For example, heart sound signals may beused to determine timings between occurrences of cardiac events. One ormore parameters that define ADS therapy may be changed to obtain adesired increase and/or decrease in these timings.

Other signals not related to pressures within the intrathoracic cavitymay also be monitored and used as a feedback mechanism to adjust ADStherapy and optimize therapy. For example, signals related to thehemodynamic effect of change, i.e. change in pulse transit time, may bemonitored. In one configuration, the time from the R wave (or other ECGfiducials) to the peak or max first derivative of the SpO2(plethysmograph) signal may be measured for various fixed timing delaysbetween the R wave (or other ECG fiducials) and the ADS pulse deliveredto the diaphragm. The results are trended and the properties of thattrend, i.e. minima and maxima are determined either algorithmicallyand/or visually by the clinician. The best setting would be the ADSdelay setting which is associated with the longest time from the R wave(or other ECG fiducials) to the max first derivative of the SpO2(plethysmograph) signal as this reflects the best cardio-vascularimpedance match and most optimal decrease in afterload for that patient.In another configuration, the time from the Q point (or other ECGfiducials) to the mitral valve component of the first heart sound (S1)is assessed for each programmed ADS delay setting, and the settingassociated with the shortest Q to S1 is then determined to be the bestsetting for the patient as it reflects the best setting at which theheart systolic function is most efficient.

Devices and Systems for ADS Therapy

As previously described, an ADS therapy delivery mechanism 100 maybe: 1) a part of a single-piece, or multi-piece standalone IMD thatdelivers only diaphragmatic stimulation therapy, 2) a part of amulti-therapy IMD that provides other therapy, such as CRM therapy, inaddition to diaphragmatic stimulation therapy, or 3) a part of anmedical system that monitors, diagnoses and treats various patientconditions.

Standalone, Multi-Piece Implantable Medical Device

With reference to FIGS. 3A and 3B, a standalone, multi-piece IMD 300that delivers only ADS therapy includes a can or housing 302 that houseselectronics and a sub-structure 304, e.g., a lead, that carries an ADStherapy delivery mechanism comprising a ring electrode 330 and a helixelectrode 332. The lead 304 is configured for implant on a surface of abiological membrane forming part of a hermetically sealed biologicalcavity. For example, the biological membrane may be a diaphragm 204 andthe hermetically sealed biological cavity may be the thoracic cavity, asdescribed above referring to FIG. 1 . In FIG. 3A the IMD 300 is locatedon the inferior side of the diaphragm 204.

The lead 304 includes a sensor assembly 306 at a distal end 308 of thelead. The sensor assembly 306 includes a housing 310, which may becylindrical in shape, that is electrically coupled to a lead body 312that extends from the distal end 308 of the lead to a connector 314 atthe proximal end 316 of the lead. The sensor assembly 306 furtherincludes a sensor structure 322. Conductive wires from the lead body 312pass through the housing 310 to connect with sensors.

The sensor structure 322 includes one or more sensors 326, 328. Thesensors may be, for example, electrodes 326 for sensing cardiacelectrical activity, or a motion sensor 328, e.g. an acoustic transducerfor sensing heart sounds, or an accelerometer for sensing mechanicalmotion of the heart and/or the diaphragm. In the case of electrodes 326,the electrodes may be flat surface electrodes or ring electrodes. In oneconfiguration, the sensor structure 322 includes a ring 330 having acircumference and one or more electrodes 326 spaced apart around thecircumference of the ring, and possibility one or more motion sensors328. In another configuration, the entirety of the ring 330 may be asingle electrode and another electrode may be located within the ring.

The sensor assembly 306 further includes one or more fixation structuresassociated with the housing 310 for securing the sensor assembly to abiological membrane. In one embodiment, the fixation structure may be aprojecting structure 332 that extends away from the housing 310 in adirection along a central axis 336 of the cylindrical housing. Forexample, the projecting structure 332 may be in the form of a helixlocated in the center of the ring 330 that forms part of the sensorstructure 322. The projecting structure 332 may be formed of anelectrically conductive material and may function both as a fixationdevice for securing the sensor assembly 306 to a biological membrane,e.g., a diaphragm, and as an additional electrode for the sensorassembly.

In another embodiment, the fixation structure may be an extension member334 that extends beyond the outer circumference of the housing 310. Tothis end, the extension member 334 has a maximum dimension, e.g.,diameter, that is greater than a maximum dimension, e.g., diameter, ofthe housing 310. The extension member 334 may be in the form of a ringthat surrounds the sensor assembly 306. As described further below, theextension member 334 may be configured in various ways to attach to thesurface of the biological membrane to secure the sensor assembly 306 inplace.

In yet another embodiment, the fixation structure may include both aprojecting structure 332 and an extension member 334. In thisembodiment, the extension member 334 surrounds the projecting structure332 and is configured to form a seal between itself and the biologicalmembrane, which seal surrounds the projecting structure. The extensionmember 334 is a generally planar structure that increases the overallsize of the contact surface area of the sensor assembly 306 around thearea where the projecting structure 332 extends into the diaphragm. Thecontact surface area corresponds to the surface area of the sensorassembly 306 that will contact the diaphragm. Upon implant of the sensorassembly 306, and over time, the diaphragm may react to the presence ofthe sensor assembly and form an adhesive bond with the sensor assembly.

The extension member 334 may include other features that help secure thesensor assembly 306 in place and/or help expedite the formation of aseal with the surface of the diaphragm. For example, the extensionmember 334 may include an adhesive that both secures the sensor assembly306 in place and forms a hermetic seal with the surface of the diaphragmaround the area where the projecting structure 332 extends into thediaphragm.

In another configuration, the extension member 334 may be formed of amaterial configured to secure the sensor assembly 306 in place and toexpedite the formation of a seal with the surface of the diaphragmaround the area where the projecting structure 332 extends into thediaphragm. For example, the extension member 334 may be a mesh materialformed of polyester textile fiber, such as Dacron, or other fabric. Uponcontact between the mesh structure 334 and the diaphragm, the meshstructure absorbs biological fluids on the surface of the diaphragm,clings to the diaphragm, and forms a seal between itself and thediaphragm.

The connector 314 of the lead includes a number of contacts 342corresponding to the number of electrodes 326 and sensors 328 associatedwith the sensor assembly 306. The lead body 312 includes conductors thatelectrically connect the contacts 342 at the proximal end 316 with thesensors 326, 328 of the sensor assembly 306.

Standalone, Single-Piece Implantable Medical Device

With reference to FIGS. 4A and 4B, a standalone, single-piece IMD 400that delivers only ADS therapy includes a housing 402 with at least twoelectrodes 404, 406 closely associated with a surface of the housing.The single-piece IMD 400 is configured for implant on a surface of abiological membrane forming part of a hermetically sealed biologicalcavity. For example, the biological membrane may be a diaphragm 204 andthe hermetically sealed biological cavity may be the thoracic cavity, asdescribed above referring to FIG. 1 . In FIG. 4A the IMD 400 is locatedon the inferior side of the diaphragm 204.

While the IMD 400 illustrated in FIG. 4B is formed is the shape of anelongated disk, the IMD may have other form factors, including forexample, a tube. The leadless IMD 400 may have a length of about1.25-inches, a width of about 0.5-inches, and a thickness of about0.125-inches. The two electrodes 404, 406 are spaced apart by about1-inch and are located on a surface 408 of the housing. Anon-electrically-conductive, biocompatible mesh 410 may be affixed tothe surface 408 to facilitate anatomical bonding of the IMD 400 to thesurface region of the diaphragm 204.

Multi-Therapy Implantable Medical Device

With reference to FIGS. 5A and 5B, a multi-therapy IMD 500 that deliversADS therapy as part of another therapy, such as CRM therapy, includes anelectronics component 502, one or more cardiac leads 504, 506, and adiaphragmatic stimulation lead 508. The one or more cardiac leads 504,506 support pacemaker functionality, defibrillation functionality, orboth. Each of the cardiac leads 504, 506 is configured to be implantedinto the heart through the subclavian vein. For example, a pacing lead506 may terminate in the right atrium, while a defibrillator lead 504extends into the right ventricle. The diaphragmatic stimulation lead 508supports ADS therapy and may configures the same as the lead 304 in FIG.3B.

The ADS therapy delivery mechanism 100 portion of the diaphragmaticstimulation lead 508 may be implanted on the superior side of thediaphragm 104 through conventional thoracotomy accessed near theinfraclavicular pocket, or through a sub-xiphoid approach by creating asubcutaneous tunnel from the location of the electronics component 502parallel to the sternum until reaching a sub sternal location from wherea laparoscopic thoracotomy is performed at a subxiphoid location toreach the superior region of the diaphragm.

The electronics component 502 may be implanted subcutaneously in asurgically created pocket at an infraclavicular pectoral region inaccordance with standard pacemaker implant procedures. The electronicscomponent 502 includes electrical componentry configured to: generatepacing pulses for pacing the heart 114 through one or more of thecardiac leads 504, 506, generate defibrillation energy pulses fordefibrillating the heart through a cardiac lead 504, and generateasymptomatic stimulation pulses for stimulating the diaphragm 104through the diaphragmatic stimulation lead 508. The electronicscomponent 502 and diaphragmatic stimulation lead 508 may includeelectrical and mechanico-electrical componentry to perform cardiacsensing functionality for purposes of cardiac synchronized diaphragmaticstimulation. Alternatively, in the case of a pacemaker, one or more ofthe cardiac leads 504, 506 may perform cardiac sensing functionality forpurposes of cardiac synchronized diaphragmatic stimulation.

Medical Device System

With reference to FIG. 6 , a medical system 600 that provides ADStherapy includes an implantable master unit 602, at least oneimplantable slave unit 604 and an external unit 606. The master unit 602determines ADS therapy configuration and controls operation of theimplantable slave unit 604 to deliver ADS therapy. The master unit 602includes sensors 608 and memory-stored algorithms 610 configured tomodify ADS therapy stimulation parameters and the timing for deliveringtherapy, based on the monitored effect of ADS therapy. The memory-storedalgorithms 610 of the master unit 602 are also configured to enable theprogramming of the ADS therapy configuration of the slave unit 604 usingthe external unit 606, e.g., programmer and user interface.

The slave unit 604 delivers ADS therapy by outputting ADS pulses throughone or more stimulators 612, e.g. electrodes, placed on the diaphragm.The slave unit 604 may be actively powered by an onboard battery orpassively powered, e.g., RF powered by master unit 602 or the externalunit 606. The slave unit 604 may be self-charging. To this end, theslave unit 604 may be configured to convert diaphragmatic motion intoenergy.

The slave unit 604 may include or be coupled to one or more sensors 614.These one or more sensors 614 may provide various signals, includingimpedance, ECG, EMG, heart sounds, diaphragmatic motion/strength,pressure (abdominal or thoracic), strain gauge, temperature, SpO2, andPH. These signals may be processed onboard the slave unit 604 by aprocessor 616 or communicated to the master unit 602 for processing. Themaster unit 602 may analyze the signals for purposes of making therapyimprovements (adjusting ADS pulse parameters and time, adjusting sensingparameters) as well as diagnostics (heart failure status, diaphragmhealth). The slave unit 604 may also communicate the sensed signals tothe external unit 606 for diagnostic purposes

Either of the master unit 602 and slave unit 604 may communicate withother implantable devices or external devices to gather furtherdiagnostic information. For example, the implantable master units 602and the implantable slave unit 604 may communicate with a deviceimplanted in the pulmonary artery (PA) to collect PA pressureinformation. The external unit 606 could also control function as a“master”, i.e. the external unit 606 could determine ADS therapyconfiguration and control operation of the implantable slave unit 604 orthe implantable master unit 602 to deliver ADS therapy.

Implantable Medical Devices with ADS Therapy

FIG. 7 is a block diagram of an IMD 700 configured to affect pressureswithin the intrathoracic cavity through delivery of ADS therapy. The IMD700 includes a controller 702, a cardiac event source 706, a pressuremeasurement source 708, and an ADS therapy delivery mechanism 100, eachof which may be coupled for interaction with the controller, eitherthrough a wired connection or through a wireless connection. Thecontroller 702 includes a cardiac signal module 728, a pressure signalmodule 730, a therapy module 740, and various other modules.

The cardiac event source 706 is configured to provide signals to thecontroller 702 that represent cardiac events. For example, the cardiacevent source 706 may be one or more electrodes 712, 714 configured to bepositioned on or near a diaphragm to sense electrical signalsrepresentative of cardiac events and to provide the signals to thecontroller 702. Alternatively, the one or more electrodes 712, 714 maybe configured to be positioned in, on, or adjacent to an intrathoracicstructure, e.g. heart, pericardium, great artery and vein, within theintrathoracic cavity. In this case, the one or more electrodes 712, 714may be associated with a device configured to be implanted remote fromthe controller 702 and to provide signals sensed by the electrodes tothe controller through a wireless communication link.

The cardiac event source 706 may also be a motion sensor 716 configuredto be positioned on or near a diaphragm to sense motion of the heart orto sense heart sounds, and to output electrical signals representativeof such motion. Alternatively, the motion sensor 716 may be configuredto be positioned in, on, or adjacent to an intrathoracic structure, e.g.heart, pericardium, great artery and vein, within the intrathoraciccavity. In this case, the motion sensor 716 may be associated with adevice configured to be implanted remote from the controller 702 and toprovide signals sensed by the motion sensor to the controller through awireless communication link. In either case, the motion sensor 716 maybe, for example, an accelerometer (such as a multi-axial e.g.,three-dimensional, accelerometer) that provides signal related to heartmovement, or an acoustic transducer that provides signal related toheart sounds.

The pressure measurement source 708 is configured to provide signals tothe controller 702 that represent one or more pressures within theintrathoracic cavity. “Pressures within the intrathoracic cavity” mayinclude an intrathoracic pressure obtained directly through a pressuresensor placed in the open space of the intrathoracic cavity and outsideof any intrathoracic structures, e.g. heart, pericardium, great arteriesand veins, within the cavity. “Pressures within the intrathoraciccavity” may also include a measure of intrathoracic pressure obtainedindirectly, for example, through an accelerometer placed outside of theintrathoracic cavity that provides a measure indicative of, orcorrelated with, intrathoracic pressure. “Pressures within theintrathoracic cavity” may also include pressures associated withintrathoracic structures like the heart, pericardium, great arteries andveins. For example, these “pressures within the intrathoracic cavity”may include right atrial pressure, right ventricular pressure, leftventricular pressure, and aortic pressure.

The pressure measurement source 708 may be one or more pressure sensors718 configured to be positioned in the open space of the intrathoraciccavity, or in, on, or adjacent an intrathoracic structure, e.g. heart,pericardium, great artery and vein, within the cavity, and configured tooutput electrical signals representative of pressure. To these ends, theone or more pressure sensors 718 may be directly coupled to thecontroller 702, or alternatively, associated with a device configured tobe implanted remote from the controller 702 and to provide signalssensed by the one or more pressure sensors to the controller through awireless communication link.

Direct coupling between the one or more pressure sensors 718 and thecontroller 702 may be appropriate when the IMD 700 is implanted on thesuperior side of the patient's diaphragm at a superior implant location122, such as shown in FIG. 1 . When implanted in this location, pressuresensors 718 directly coupled to the controller 702 would be placed inthe open space of the thoracic cavity 102. Remote coupling between theone or more pressure sensors 718 and the controller 702 may beappropriate when the IMD 700 is implanted on the inferior side of thepatient's diaphragm at an inferior implant location 120, such as shownin FIG. 1 . When implanted in this location, one or more pressuresensors 718 separately implanted in the intrathoracic cavity andremotely coupled to the controller 702 may provide pressure signals. Forexample, the pressure sensor 718 may be included in a device configuredto be implanted: 1) in the right atrium to obtain right-atrial pressuresignals, 2) in the right ventricle to obtain right ventricularpressures, 3) in the right ventricle to obtain surrogates of pulmonaryartery pressure, or 4) within the pulmonary artery itself.

The pressure measurement source 708 may also be a motion sensor 720configured to provides signals indicative of, or that correlate to,intrathoracic pressure. For example, the motion sensor 720 may be anaccelerometer configured to be positioned on or near a diaphragm tosense motion of the diaphragm, and to output electrical signalsrepresentative of such motion to the controller 702. As will bedescribed further below, fluctuations in these electrical signalscorrelate to changes in intrathoracic pressure associated withrespiration cycles. The motion sensor 720 may also be an accelerometeror acoustic transducer configured to be positioned within the patient tosense sounds associated with cardiac function, and to output electricalsignals representative of such sounds. Fluctuations in these electricalsignals correlate to changes in intrathoracic pressure associated withrespiration cycles. Alternatively, the motion sensor 720 may be animpedance/conductance sensor in the form of a pair of electrodesconfigured to be positioned in or on the diaphragm, and to outputelectrical signals representative of impedance or conductance ofdiaphragm tissue. Fluctuations in impedance or conductance correlate tochanges in expansion and contraction of the diaphragm, which in turncorrelate to changes in intrathoracic pressure associated withrespiration cycles.

The ADS therapy delivery mechanism 100 is configured to applystimulation to the diaphragm to cause asymptomatic, transient, partialcontraction of the diaphragm. As previously mentioned, a “transient”contraction of the diaphragm is a short, twitching, caudal followed bycranial motion of the diaphragm that lasts in range of 60 to 180 msec.,and is typically about 100 msec. A “partial” contraction of thediaphragm is the part or portion of the diaphragm (less than theentirety of the diaphragm) that exhibits a “transient” contraction. Thestimulation is characterized by a set of stimulation parameters thatinduce a partial contraction of the diaphragm that does not affectrespiration. More specifically, the stimulation is configured such thatthe diaphragm does not contract to a level that induces inspiration. TheADS therapy delivery mechanism 100 may be one or more electrodes 722,724 configured to be positioned on or near a diaphragm to deliverelectrical stimulation pulses to the diaphragm.

Considering the controller 702 in more detail, the cardiac signal module728 of the controller receives signals from the cardiac event source 706and is configured to process the signals to detect cardiac events ofinterest. For example, as will be described further below, the cardiacsignal module 728 may be configured to detect one or more of anelectrical cardiac event, such as a ventricular depolarizationrepresented by an R-wave, and 2) a mechanical cardiac event, such as aventricular contraction represented by an S1 heart sound. Informationcorresponding to detected cardiac events is provided to the therapymodule 740, which in turn processes the cardiac-event information todetermine or adjust one or more parameters of a stimulation therapy.

With respect to electrical cardiac events, the cardiac signal module 728may include an electrogram (EGM) analysis module 732 adapted to receiveelectrical signals from the electrodes 712, 714 and to process theelectrical signals to detect cardiac events of interest. The EGManalysis module 732 may be configured to process a cardiac electricalactivity signal, e.g., an EGM signal, to detect cardiac eventscorresponding to atrial events, such as P waves, or ventricular events,such as R waves, QRS complexes, or T waves.

Regarding mechanical cardiac events, the cardiac signal module 728 mayinclude a heart motion/sounds analysis module 734 for analyzingmechanical motion of the heart. The heart motion/sounds analysis module734 is adapted to receive signals from the motion sensor 716 and todetect a cardiac event of interest. As previously mentioned, the motionsensor 716 may be, for example, an accelerometer or acoustic transducer,configured to sense a variety of mechanical and sound activities, suchas diaphragm motion and heart sounds. Heart sound signals obtainedthrough the accelerometer may be processed by the heart motion/soundsanalysis module 734 to detect cardiac events.

The pressure signal module 730 of the controller 702 receives signalsfrom the pressure measurement source 708 and is configured to processthe signals for purposes of detecting a pressure event of interest orderiving a pressure measure of interest. For example, regarding measuresof interest, the pressure signal module 730 may process signals from apressure sensor 718 to determine pressure measurements under differenttherapy conditions, e.g., with diaphragmatic stimulation on, and withdiaphragmatic stimulation off, or under different stimulation settings.The pressure signal module 730 may also process signals from a pressuresensor 718 to determine pressure measurements at different times, e.g.,at or near delivery of a stimulation pulse, and at or near an occurrenceof a particular cardiac event. Regarding events of interest, thepressure signal module 730 may process signals from a motion sensor 720to detect respiration cycles and to identify one or more events ofinterest within the cycle, such as end inspiration. Informationcorresponding to detected events of interest and measures of interest,collectively referred to as pressure information, is provided to thetherapy module 740. The therapy module 740, in turn, processes thepressure information to determine whether an adjustment to one or moreparameters of a stimulation therapy is warranted.

Regarding the processing of signals from a pressure sensor 718, thepressure signal module 730 may include a pressure measurement module 736for analyzing pressures within the intrathoracic cavity. The pressuremeasurement module 736 is adapted to receive signals from the pressuresensor 718. As previously described, the pressure sensor 718 may be aconfigured to be placed in the open space of the intrathoracic cavityand outside of any intrathoracic structures, e.g. heart, pericardium,great arteries and veins, within the cavity—to thereby provide a signalrepresenting intrathoracic pressure. Alternatively, the pressure sensor718 may be configured to be placed in, on, or adjacent an intrathoracicstructure, e.g. heart, pericardium, great artery and vein, within thecavity. For example, the pressure sensor 718 may be configured to beplaced in, on, or adjacent to one of the right atrium, the rightventricle, the left ventricle, the aorta, and the pulmonary artery—tothereby provide a corresponding signal presenting right atrial pressure,right ventricular pressure, left ventricular pressure, aortic pressure,or pulmonary artery pressure.

The pressure measurement module 736 is further adapted to processsignals obtained from the pressure sensor 718 to derive pressuremeasures of interest. The pressure measurement is provided to thetherapy module 740, where it is further processed to determine ifstimulation therapy may be improved to provide a more desirable outcome.For example, different measures of intrathoracic pressure may beobtained for different stimulation therapies, each defined by adifferent set of stimulation parameter values, to determine which set ofstimulation parameters provides the best measure of intrathoracicpressure. In another example, the measure of intrathoracic pressure maybe compared to a predetermine threshold value, to determine if one ormore of the stimulation parameters should be adjusted in an attempt toobtain, or at least more closely approach, the threshold value.

Regarding the processing of signals from a motion sensor 720, thepressure signal module 730 may include a diaphragm motion and heartsounds analysis module 738 for analyzing one or more of motion of thediaphragm and sounds associated with the heart. The diaphragm motion andheart sounds analysis module 738 is adapted to receive signals from themotion sensor 720 and to detect a pressure event of interest. Aspreviously described, the motion sensor 720 may be an accelerometerconfigured to be positioned on or near a diaphragm to sense motion ofthe diaphragm. The motion sensor 720 may also be an accelerometer or anacoustic transducer configured to be positioned within the patient tosense sounds associated with cardiac function, and to output electricalsignals representative of such sounds. Alternatively, the motion sensor720 may be an impedance/conductance sensor in the form of a pair ofelectrodes configured to be positioned in or on the diaphragm.

Regarding the therapy module 740, it includes a cardiac-event analysismodule 742, a pressure analysis module 744, and a pulse generator 746.The pulse generator 746 is configured to output stimulation therapy tothe ADS therapy delivery mechanism 100. The stimulation therapy may bein the form of electrical stimulation, in which case the therapy may bedelivered through electrodes 722, 724.

The stimulation therapy output by the pulse generator 746 is defined byone or more stimulation parameters. For electrical stimulation, theparameters may include: 1) one or more pulse parameters having a valueor setting selected to define a stimulation pulse that induces atransient, partial contraction of the diaphragm, and 2) a timingparameter that controls the timing of the delivery of one or morestimulation pulses. The pulse parameters may include, for example, apulse waveform type, a pulse amplitude, a pulse duration, and a pulsepolarity. The timing parameter may include one or more offset periods ordelay periods that define a time between a detected cardiac event and adelivery of an electrical stimulation pulse.

One or more of the stimulation parameters, including timing parametersand pulse parameters, may be adjusted by the therapy module 740. Withrespect to timing parameters, as previously mentioned, the rate ofelectrical stimulation may be adjusted in response to changes in theheart rate of the patient. Accordingly, the rate of delivery ofelectrical stimulation pulses may range, for example, between 30 pulsesper minute (ppm) and 180 ppm, with a typical rate being around 60 ppm.Likewise, a delay period between a detected cardiac event and a deliveryof an electrical stimulation pulse may be adjusted based on a runningaverage of time intervals between detected cardiac events. Regardingpulse parameters, the pulse amplitude may be set to a value between 0.0volts and 7.5 volts, and the pulse width may be set to a value between0.0 milliseconds and 1.5 milliseconds. The amplitude may be adjusted,for example, in increments of between 0.1 to 0.5 volts, while the pulsewidth may be adjusted in increments of between 0.1 to 1.5 milliseconds.The polarity may be changed between a positive polarity and a negativepolarity, and the waveform type may be changed from mono-phasic tobiphasic, or from a square to a triangular, sinusoidal or sawtoothwaveform.

The cardiac-event analysis module 742 is configured to receivecardiac-event information from the cardiac signal module 728 and toprocess the information to determine the timing parameter. To this end,in one configuration, the cardiac-event analysis module 742 determines atime, relative to a detected cardiac event, at which to deliver astimulation pulse to the diaphragm. The determined time, referred to asa delay period, may be selected so that the stimulation pulse isdelivered just prior to the next expected occurrence of the cardiacevent.

The offset periods or delay periods may be based on the time betweensuccessive detected cardiac events. For example, the EGM analysis module732 of the cardiac signal module 728 may be configured to detectventricular events, e.g., R waves, and to output such detections to thetherapy module 740. The cardiac-event analysis module 742 may processthe detected ventricular events to determine a statistical measure oftime between a number of pairs of successive ventricular events. Thecardiac-event analysis module 742 may then determine one or more offsetperiods or delay periods based on the statistical measure, and controlthe pulse generator 746 to output stimulation pulses based on thedetermined offset period or delay period.

The pressure analysis module 744 of the therapy module 740 is configuredto receive pressure information, including one or more of a measure ofinterest, e.g., a pressure measurement, or an event of interest, e.g.,end inspiration of a respiration cycle, from the pressure signal module730. The pressure analysis module 744 is further configured to processthe received pressure information to determine if an adjustment of astimulation parameter is warranted.

In one configuration, the pressure analysis module 744 may receivepressure information corresponding to a measure of interest, and mayevaluate the measure of interest against a baseline measure of interest.For example, the received measure of interest may be a measure of anintrathoracic pressure, RA pressure, RV pressure, Ao pressure, or LVpressure at a fiducial point. The pressure analysis module 744 maycompare the received measure of interest to the baseline to determine ifthe comparison outcome is acceptable. If the comparison outcome is notacceptable, the therapy module 740 may adjust one or more stimulationparameters for future stimulation therapy to eventually arrive at astimulation therapy that results in an acceptable outcome.

In another configuration, the pressure analysis module 744 may receivepressure information corresponding to an occurrence of a pressure eventof interest. The pressure event of interest may, for example, relate torespiration cycles of a patient and may be a point of end inspirationwithin a respiration cycle. In response to the receipt of such pressureinformation, the pressure analysis module 744 may determine to withholdstimulation therapy or to change one or more stimulation parameters.

The controller 702 includes a memory subsystem 748. The memory subsystem748 is coupled to the cardiac signal module 728 and the pressure signalmodule 730, and may receive and store data representative of sensedEGMs, sensed intrathoracic cavity pressure, heart sounds, and sensedcardiovascular pressures, e.g., right ventricular pressures, leftventricular pressure, right atrial pressure, and aortic pressure. Thememory subsystem 748 is also coupled to the therapy module 740 and mayreceive and store data representative of delivered stimulationtherapies, including their associated sets of stimulation parameters andtimes of delivery.

The controller 702 also includes a communication subsystem 750 thatenables communication between the controller and other components. Theseother components may form part of the IMD 700, such an a separatelyimplanted pressure sensor within the intrathoracic cavity, may beseparate from the IMD, such as an external programmer used by aphysician to program the IMD. The communication subsystem 750 mayinclude a telemetry coil enabling transmission and reception of signals,to or from an external apparatus, via inductive coupling. Alternativeembodiments of the communication subsystem 750 could use an antenna foran RF link, or a series of low amplitude high frequency electricalpulses emitted by the sensor that do not illicit muscle or nervousactivation, detected by sensing electrodes of the stimulating IMD. Thecontroller 702 also includes a power supply 752 that supplies thevoltages and currents necessary for each module of the controller, and aclock supply 754 that supplies the modules with any clock and timingsignals.

Regarding the physical structure of the IMD 700, while the foregoingfunctional description of the IMD describes separate pairs of electrodes712, 714 and 722, 724, respectively associated with the cardiac eventsource 706 and the ADS therapy delivery mechanism 100, a configurationof the IMD may include a single pair of electrodes configured to performdual functions. That is, the IMD 700 may include a single pair ofelectrodes configured to both sense cardiac electrical activity and todeliver electrical stimulation. In this configuration, the controller702 may include an electrode interface that is configured to switch theconnection of the electrodes between the cardiac event source 706 andthe ADS therapy delivery mechanism 100 as needed. The electrodeinterface may also provide other features, capabilities, or aspects,including but not limited to amplification, isolation, andcharge-balancing functions, that are required for a proper interfacebetween the electrodes and diaphragm tissue.

Similarly, the respective functions of the separate motion sensors 716,720 referenced with respect to the cardiac event source 706 and thepressure measurement source 708 may be provided by a single motionsensor shared by the different sources. In this configuration, thecontroller 702 may include sensor interface that is configured to switchthe connection of the single sensor between the cardiac event source 706and the pressure measurement source 708 if needed. The sensor interfacemay also provide other features, capabilities, or aspects, including butnot limited to amplification, isolation, that are required for a properinterface between the sensor and diaphragm tissue.

The cardiac signal module 728, the pressure signal module 730, and thetherapy module 740 of the IMD 700 include or are associated with one ormore processors configured to access and execute computer-executableinstructions stored in memory associated with the modules. The one ormore processors may include a central processor of the controller 702that executes instructions for all modules 728, 730, 740. Alternatively,each of the various modules 728, 730, 740 may have a dedicatedprocessor. Instructions executed by the one or more processor may bestored in the memory subsystem 748 or in one or more additional memorycomponents (not shown) of the controller 702.

The one or more processors of the controller 702 may be implemented asappropriate in hardware, software, firmware, or combinations thereof.Software or firmware implementations of the one or more processor of thecontroller 702 may include computer-executable or machine-executableinstructions written in any suitable programming language to perform thevarious functions described herein. The one or more processors of thecontroller 702 may include, without limitation, a central processingunit (CPU), a digital signal processor (DSP), a reduced instruction setcomputer (RISC) processor, a complex instruction set computer (CISC)processor, a microprocessor, a microcontroller, a field programmablegate array (FPGA), a System-on-a-Chip (SOC), or any combination thereof.The IMD 700 may also include a chipset (not shown) for controllingcommunications between the one or more processors of the controller 702and one or more of the other components of the IMD 700. The one or moreprocessors of the controller 702 may also include one or moreapplication-specific integrated circuits (ASICs) or application-specificstandard products (ASSPs) for handling specific data processingfunctions or tasks.

The memory subsystem 748 and any other memory components of the IMD 700may include, but is not limited to, random access memory (RAM), flashRAM, magnetic media storage, optical media storage, and so forth. Thememory subsystem 748 and other memory components may include volatilememory configured to store information when supplied with power and/ornon-volatile memory configured to store information even when notsupplied with power. The memory subsystem 748 and other memorycomponents of may store various program modules, application programs,and so forth that may include computer-executable instructions that uponexecution by the one or more processors of the controller 702 may causevarious operations to be performed. The memory subsystem 748 and othermemory components may further store a variety of data manipulated and/orgenerated during execution of computer-executable instructions by thevarious modules 728, 730, 740 of the controller 702.

As previously described, the IMD 700 may further include a communicationsubsystem 750 that may facilitate communication between the IMD 700 andone or more other devices using any suitable communications standard.For example, a LAN interface may implement protocols and/or algorithmsthat comply with various communication standards of the Institute ofElectrical and Electronics Engineers (IEEE), such as IEEE 802.11, whilea cellular network interface implement protocols and/or algorithms thatcomply with various communication standards of the Third GenerationPartnership Project (3GPP) and 3GPP2, such as 3G and 4G (Long TermEvolution), and of the Next Generation Mobile Networks (NGMN) Alliance,such as 5G.

The memory subsystem 748 and other memory components may store variousprogram modules, algorithms, and so forth that may includecomputer-executable instructions that upon execution by the one or moreprocessors associated with the various modules 728, 730, 740 of thecontroller 702 may cause the various operations of these modules, asdescribed above and further below, to be performed. To this end, thememory subsystem 748 and other memory components storecomputer-executable instructions that enable a processor to perform: 1)the EGM analysis and heart motion analysis operations of the cardiacsignal module 728, 2) the pressure measurement and diaphragmmotion/heart sounds analysis operations of the pressure signal module730, and 3) the cardiac-event analysis, pressure analysis, and EMGanalysis of the therapy module 740.

The memory subsystem 748 and other memory components also storecomputer-executable instructions that enable a processor associated withthe therapy module 740 to perform the signal processing, analysis, andADS therapy delivery associated with each of: 1) the dual-pulse ADStherapy disclosed further below, 2) the paired-pulse ADS therapydisclosed further below, 3) multiple pulse ADS therapy disclosed furtherbelow, and 4) the EGM monitoring and health assessment disclosed furtherbelow.

The various modules 728, 730, 740 of the controller 702 may beimplemented in hardware or software that is executed on a hardwareplatform. The hardware or hardware platform may be a general purposeprocessor, a digital signal processor (DSP), an application specificintegrated circuit (ASIC), a field programmable gate array (FPGA) orother programmable logic component, discrete gate or transistor logic,discrete hardware components, or any combination thereof, or any othersuitable component designed to perform the functions described herein. Ageneral-purpose processor may be a microprocessor, but in thealternative, the processor may be any conventional processor,controller, microcontroller, or state machine. A processor may also beimplemented as a combination of computing components, e.g., acombination of a DSP and a microprocessor, a plurality ofmicroprocessors, one or more microprocessors in conjunction with a DSP,or any other such configuration.

Software shall be construed broadly to mean instructions, instructionsets, code, code segments, program code, programs, subprograms, softwaremodules, applications, software applications, software packages,routines, subroutines, objects, executables, threads of execution,procedures, functions, etc., whether referred to as software, firmware,middleware, microcode, hardware description language, or otherwise. Thesoftware may reside on a computer-readable medium. A computer-readablemedium may include, by way of example, a smart card, a flash memorydevice (e.g., card, stick, key drive), random access memory (RAM), readonly memory (ROM), programmable ROM (PROM), erasable PROM (EPROM),electrically erasable PROM (EEPROM), a general register, or any othersuitable non-transitory medium for storing software.

ADS Therapy Algorithms

Having thus described the structural components of an IMD 700, and theirrespective functions, a description of several ADS therapy algorithmsimplemented by the IMD are described.

One algorithm relates to ADS therapy where a single stimulation pulse isdelivered to the diaphragm per cardiac cycle. Another algorithm relatesto ADS therapy where dual stimulation pulses are delivered to thediaphragm per cardiac cycle, one during the diastolic phase of thecardiac cycle and the other during the systolic phase. Another algorithmrelates to ADS therapy where a pair of closely spaced stimulation pulsesare delivered to control the duration of diaphragm movement in aparticular direction, e.g., cranial direction or caudal direction. Yetanother algorithm relates to ADS therapy where multiple stimulationpulses are delivered to the diaphragm at a cardiac-cycle specificfrequency based on heart rate, to cause a permanent partial mechanicalmodulation of the diaphragm.

Single Pulse ADS Therapy

ADS therapies that deliver a single ADS pulse per cardiac cycle aredisclosed, for example, in U.S. Pat. No. 10,315,035, titled “HemodynamicPerformance Enhancement Through Asymptomatic Diaphragm Stimulation” andU.S. Pat. No. 10,335,592, titled “Systems, Devices, and Methods forImproving Hemodynamic Performance Through Asymptomatic DiaphragmStimulation.”

Dual-Pulse ADS Therapy

Dual-pulse ADS therapy is a therapy where multiple, e.g., two,asymptomatic stimulation pulses are delivered to the diaphragm percardiac cycle. This ADS therapy results in multiple transient, partialcontractions of the diaphragm per cardiac cycle, which translates intoan intrathoracic pressure modulation most favorable for the optimizationof preload and afterload in support of the patient's hemodynamics. Aspreviously mentioned, a “transient” contraction of the diaphragm is ashort, twitching, caudal followed by cranial motion of the diaphragmthat lasts in the range of 60 to 180 msec., and is typically about 100msec. A “partial” contraction of the diaphragm is the part of thediaphragm (less than the entirety of the diaphragm) that exhibits a“transient” contraction.

With reference to FIGS. 8A and 8B, in one embodiment, at least twodiaphragmatic stimulation pulses 802, 804 are delivered per cardiaccycle 806. The delivery of each stimulation pulse 802, 804 issynchronized to a cardiac event so that one stimulation pulse 802 isdelivered in the latter part of diastole (preload benefit) of thecardiac cycle 806 and the other stimulation pulse 804 is delivered atthe early part of systole (afterload benefit) of the cardiac cycle. Asshown in FIG. 8B, each of these stimulation pulses 802, 804 causes acorresponding transient, partial contraction 808, 809 of the diaphragm,each comprising a movement in the caudal direction followed by amovement in the cranial direction.

Referring to FIG. 8A, “the latter part of diastole” may be the atrialfilling window (between a P wave and following Q point), with thecorresponding stimulation pulse 802 preferably being delivered closer tothe Q point than the P wave. The “early part of systole” may be thesystolic output (between a S1 heart sound and following S2 heart sound),with the corresponding stimulation pulse 804 preferably being deliveredat an offset of about 50-100 msec. after the mitral valve component ofthe S1 heart sound.

The triggering of the two diaphragmatic stimulation pulses 802, 804 maybe timed relative to a sensed occurrence of a valid cardiac event. Inone embodiment, delivery of each of the two diaphragmatic stimulationpulses 802, 804 is triggered by the same sensed occurrence of a cardiacevent. In another embodiment, one of the two diaphragmatic stimulationpulses 802, 804 is triggered by a sensed occurrence of a valid cardiacevent and the other of the two diaphragmatic stimulation pulses 802, 804is triggered by a sensed occurrence of another cardiac event differentfrom the one that triggered the other diaphragmatic stimulation pulse.

A valid cardiac event may be a valid ventricular event (V-event) or avalid atrial event (A-event). The sensed occurrence of a valid cardiacevent may correspond to an electrical cardiac event or a mechanicalcardiac event. Electrical cardiac events may be a feature of an ECG,such as a P wave, a QRS complex, a Q point of a QRS complex, a R wave, aS point of a QRS complex or a T wave. Mechanical cardiac events may be aS1 heart sound, a S2 heart sound, a S3 sound or a S4 heart sound.

A valid V-event may be an electrical or mechanical event of a ventriclesensed either electrically or mechanically by an IMD. In oneconfiguration, a valid electrical V-event may be an intrinsicdepolarization of the ventricle that results from normal electricalconduction through the atrioventricular (AV) node. In electrocardiogram(ECG) terminology, such a valid electrical V-event may be a normal Rwave, a normal QRS complex, or a normal T wave. In anotherconfiguration, a valid electrical V-event may be a ventricular pacingstimulus delivered to the ventricle and sensed by the IMD. In yetanother configuration, a valid electrical V-event may be an evokedresponse of the ventricle sensed by the IMD. In this regard, an evokedventricular event corresponds to an electrical depolarization of theventricle that results from the delivery of a ventricular pacingstimulus.

Associated with a ventricular depolarization, whether intrinsic orevoked, is a physical contraction of the ventricle. Accordingly, each ofan intrinsic ventricular depolarization and an evoked ventriculardepolarization may be sensed by a mechanical sensor, e.g., in the formof an S1 heart sound or an S2 heart sound. In some cases, the IMD may beprogrammed to consider what would otherwise be a valid V-event, as anon-valid V-event if that V-event is associated with a non-normalcardiac episode. For example, if the otherwise valid V-event occursduring an episode of ventricular fibrillation or is followed by apremature ventricular contraction, the IMD may deem that V-eventnon-valid for purposes of delivering diaphragmatic stimulation.

A valid A-event may be an electrical event of an atrium, sensed eitherelectrically or mechanically by an IMD. In one configuration, a validelectrical A-event may be an intrinsic depolarization of the atrium thatoriginates from the sinoatrial (SA) node. In ECG terminology, such avalid electrical A-event may be a normal P wave. In anotherconfiguration, a valid electrical A-event may be an atrial pacingstimulus delivered to the atrium and sensed by the IMD. In yet anotherconfiguration, a valid electrical A-event may be an evoked response ofthe atrium sensed by the IMD. In this regard, an evoked atrial eventcorresponds to an electrical depolarization of the atrium that resultsfrom the delivery of an atrial pacing stimulus.

Associated with atrial depolarization, whether intrinsic or evoked, is aphysical contraction of the atrium. Accordingly, each of an intrinsicatrial depolarization and an evoked atrial depolarization may be sensedby a mechanical sensor, e.g., in the form of an S4 heart sound. In somecases, the IMD may be programmed to consider what would otherwise be avalid A-event, as a non-valid A-event if that A-event is associated witha non-normal cardiac episode. For example, if the otherwise validA-event occurs during an episode of atrial tachycardia, atrialfibrillation, or atrial flutter, the IMD may deem that A-event non-validfor purposes of delivering diaphragmatic stimulation.

With reference to FIG. 8A, the triggering of the two diaphragmaticstimulation pulses 802, 804 is timed relative to the same sensedoccurrence of an intrinsic R-wave, with one stimulation pulse 802delivered in accordance with a calculated negative offset from theR-wave for the late diastolic pulse, and the other stimulation pulse 804delivered in accordance with a calculated positive offset to be in theearly systolic part. The calculation could be a either a valuedetermined and programmed by the clinician or an actual calculationperformed by an IMD 700 based on time intervals between ECG and/or heartsound signal fiducial points.

Regarding calculations performed by an IMD 700, in accordance withembodiments disclosed herein, the timings of the delivery ofdiaphragmatic stimulation pulses 802, 804 may be determined based onsensed occurrences of cardiac events that occur over a number of cardiaccycles 806. For example, a VV interval 810 may be measured over a numberof cardiac cycle 806 to obtain an average VV interval. Based on thisaverage VV interval the IMD 700 may calculate a set of offset periods,including a first offset period 812 that defines when a firstdiaphragmatic stimulation pulses 802 is delivered relative to a cardiacevent 816, and a second offset period 814 that defines when a seconddiaphragmatic stimulation pulses 804 is delivered relative to thecardiac event 816. The first offset period 812 is characterized by anegative offset relative to the cardiac event 816 and may be describedas an “early” or “anticipatory” stimulation in that it occurs before thecardiac event. The second offset period 814 is characterized by apositive offset relative to the cardiac event 816 and may be describedas a “late” stimulation in that it occurs after the cardiac event.

The value of the first offset period 812 is selected so that the firststimulation pulse 802 is delivered during late diastole. To this end,the IMD 700 may sense occurrences of other cardiac events to determine avalue that results in such placement. For example, with reference toFIG. 8A, the IMD 700 may sense P waves 821 and Q points 822 over thesame number of cardiac cycles 806 that it senses R waves 816. Based onthe respective timing differences between the P wave 821 and R wave 816and the Q point 822 and R wave, over a number of cardiac cycles 806, theIMD 700 may calculate a first offset period 812 that places delivery ofthe first stimulation pulse 802 somewhere between the P wave 821 and Qpoint 822 that are prior to the R wave 816. In one embodiment the firststimulation pulse 802 is placed so that it is closer to Q point 822 thanit is to the P wave 821.

The value of the second offset period 814 is selected so that the secondstimulation pulse 804 is delivered during early systole. To this end,the IMD 700 may sense occurrences of other cardiac events to determine avalue that results in such placement. For example, with reference toFIG. 8A, the IMD 700 may sense S1 heart sounds 824 and T waves 826 overthe same number of cardiac cycles 806 that it senses R waves 816. Basedon the respective timing differences between the S1 heart sound 824 andR wave 816 and the T wave 826 and R wave, over a number of cardiac cycle806, the IMD 700 may calculate a second offset period 814 that placesdelivery of the second stimulation pulse 804 somewhere between the S1heart sound 824 and the T wave 826 that are after the R wave 816. In oneembodiment the second stimulation pulse 804 is placed so that it iscloser to the S1 heart sound 824 than it is to the T wave 826.

Regarding the early stimulation 802, the delivery of this stimulation istriggered by the sensed occurrence of the previous cardiac event 818. Inother words, upon detection of the cardiac event 818, the diaphragmaticstimulation pulse 802 is delivered a delay period 820 after suchdetection that places the pulse in late diastole. To this end, the IMD700 may calculate the delay period 820 as the difference between the VVinterval 810 and the first offset period 812.

While the foregoing description has focused on the delivery of dualstimulation pulses 802, 804 timed to occur respectively during diastoleand systole based on a detection of the same cardiac event, e.g., an Rwave, the delivery of these stimulation pulses may be timed to occurduring diastole and systole based on detections of other cardiac events.

In some cases, it may be desirable to simulate the diaphragm based oncertain diastole cardiac events, such as an offset of passive leftventricular filling or an onset of atrial filling, the occurrences ofwhich generally coincide with a P wave of an ECG. To this end, the IMD700 may monitor the time between a P wave 821 and a following Q point822 over a number of cardiac cycles 806, and calculate an offset from aP wave that places a delivery of a stimulation pulse 802 after the Pwave 821 but before the following Q point 822. Once this offset itdetermined, subsequent detections of these diastole cardiac events by anIMD 700 may trigger a delivery of a stimulation pulse 802 during latediastole.

In some cases, it may be desirable to simulate the diaphragm based oncertain systole cardiac events, such as: 1) an onset of electricalsystole or an offset of atrial filling, the occurrences of whichgenerally coincide with a Q point 822 of an ECG; 2) an offset ofelectrical systole, the occurrences of which generally coincide with a Twave 826 of an ECG; 3) an onset of mechanical systole, the occurrencesof which generally coincide with a S1 heart sound 824; 4) an offset ofmechanical systole or an onset of passive left ventricular filling, theoccurrences of which generally coincide with a S2 heart sound 828; 5) anonset of left ventricular systolic output, the occurrences of whichgenerally coincide with a mitral valve component of a S1 heart sound824; 6) an offset of left ventricular systolic output, the occurrencesof which generally coincide with an aortic valve component of a S2 heartsound 828; 7) an onset of right ventricular systolic output, theoccurrence of which generally coincide with a tricuspid valve componentof a S1 heart sound 824; or 8) an offset of right ventricular systolicoutput, the occurrences of which generally coincide with a pulmonicvalve component of a S2 heart sound 828.

To this end, the IMD 700 may monitor the time between one of a Q point822 or an S1 heart sound 824 and a following one of a T wave 826 or a S2heart sound 828 over a number of cardiac cycles 806, and calculate anoffset from of a Q point 822 or an S1 heart sound 824 that place adelivery of a stimulation pulse 804 after the Q point but before the Twave, or after the S1 heart sound but before the S2 heart sound. Oncethis offset it determined, subsequent detections of these systolecardiac events by an IMD 700 may trigger a delivery of a stimulationpulse 804 during early systole.

As shown in FIG. 8B, the relative timing of the first ADS pulse 802 andthe second ADS pulse 804 results in two separate and distinct transient,partial contraction 808, 809 of the diaphragm. Each of these partialcontractions 808, 809 include a caudal phase 830 corresponding to amovement in the caudal direction, followed by cranial phase 832corresponding to a movement in the cranial direction.

FIG. 9 is a flowchart of a method of affecting pressure in anintrathoracic cavity of a patient through delivery of dual ADS pulsesper cardiac cycle. The method may be performed by the IMD 700 of FIG. 7or a similar apparatus or system. For example, the method may beperformed by an apparatus having one or more electrodes 722, 724configured for placement on or near a diaphragm and a controller 702coupled to the one or more electrodes. The controller 702 is configured,for example, though executable program instructions stored in a memory,to perform the method described below with reference to FIG. 9 .

At block 902, and with additional reference to FIGS. 8A and 8B, adiastolic stimulation pulse 802 is delivered to a diaphragm of thepatient during a diastolic phase of a cardiac cycle 806 of the patient.The diastolic stimulation pulse 802 results in an asymptomatic,transient, partial contraction 840 of the diaphragm during a diastolicphase 842 of the cardiac cycle 806.

Delivery of the diastolic stimulation pulse 802 may be timed to acardiac event. To this end, an occurrence of a first cardiac event 818is detected, and the diastolic stimulation pulse 802 is delivered at ornear the end of a diastolic offset period 820 from the detected firstcardiac event. The diastolic offset period 820 places the delivery ofthe diastolic stimulation pulse 802 at a latter part of diastole of thecardiac cycle 806.

The diastolic offset period 820 may be determined by detecting, over aplurality of cardiac cycles, a time of occurrence of: a) the firstcardiac event 818, and b) one of an onset of an atrial event 821, e.g.,a detected P wave, and an offset of a first ventricular event 821, e.g.,also a detected P wave, and c) an onset of a second ventricular event822, 824 that follows the onset of the atrial event and the onset of thefirst ventricular event. The onset of a second ventricular event maycorrespond to a detected Q point 822 in a QRS complex, or a detected S1heart sound 824. The respective times of occurrences are processed tocalculate a period of time from the first cardiac events 818 to a timebetween a) either of an onset of an atrial event 821 or an offset of afirst ventricular event 821, and b) an onset of a second ventricularevent 822, 824 that follows the onset of the atrial event and the onsetof the first ventricular event. The calculated period of timecorresponds to the diastolic offset period 820.

At block 904, a systolic stimulation pulse 804 is delivered to thediaphragm during a systolic phase of the cardiac cycle 806. The systolicstimulation pulse 804 results in an asymptomatic, transient, partialcontraction 844 of the diaphragm during a systolic phase 846 of thecardiac cycle 806.

Delivery of the systolic stimulation pulse 804 may also be timed to acardiac event. To this end, an occurrence of a second cardiac event 816is detected, and the systolic stimulation pulse 804 is delivered at ornear the end of a systolic offset period 814 from the detected secondcardiac event 816. The systolic offset period 814 places the delivery ofthe systolic stimulation pulse 804 at an early part of systole of thecardiac cycle 806.

The systolic offset period 814 may be determined by detecting, over aplurality of cardiac cycles, a time of occurrence of: a) the secondcardiac event 816, and b) one of an onset of electrical systole 822,e.g., a detected Q point, and an onset of mechanical systole 824, e.g.,a detected S1 heart sound, and c) one of an offset of electrical systole826, e.g., a detected T wave, and an offset of mechanical systole 828,e.g., a detected S2 heart sound. The respective times of occurrences areprocessed to calculate a period of time from the second cardiac events816 to a time between: a) either of an onset of electrical systole 822or an onset of mechanical systole 824, and b) either of an offset ofelectrical systole 826 or an offset of mechanical systole 828. Thecalculated period of time corresponds to the systolic offset period 814.

While in the foregoing description, the second cardiac event 816 in FIG.8A that triggers delivery of the systolic stimulation pulse 804 isdifferent from the first cardiac event 818 that triggers delivery of thediastolic stimulation pulse 802, the first cardiac event and the secondcardiac event may be the same event within a same cardiac cycle. Forexample, delivery of each of the diastolic stimulation pulse 802 and thesystolic stimulation pulse 804 may be timed to a detection of a P wave821.

In other embodiments, the first cardiac event 818 that triggers deliveryof a diastolic stimulation pulse 802 and the second cardiac event 816that triggers delivery of a systolic stimulation pulse 804, may be thesame cardiac event type in consecutive cardiac cycles. In the example ofFIG. 8A, the first cardiac event 818 is a detected R wave from a priorcardiac cycle that triggers the diastolic stimulation pulse 802 in thecurrent cardiac cycle 806, while the second cardiac event 816 is adetected R wave in the current cardiac cycle that triggers the diastolicstimulation pulse 802 in the current cardiac cycle 806. While the firstand second cardiac events are electrical events, e.g., R waves, thefirst and second cardiac events may be mechanical events, e.g., an S1heart sound.

In other embodiments, the first cardiac event that triggers delivery ofa diastolic stimulation pulse 802 and the second cardiac event thattriggers delivery of a systolic stimulation pulse 804, may be differentcardiac events in a same cardiac cycle. For example, with reference toFIG. 8A, the first cardiac event may be a detected P wave 821 in thecurrent cardiac cycle 806, while the second cardiac event 816 may be adetected R wave in the current cardiac event. Again, while the first andsecond cardiac events may be electrical events, e.g., P wave, and Rwave, one or more of the first and second cardiac events may be amechanical event, e.g., an S1 heart sound.

Paired-Pulse ADS Therapy

With reference to FIG. 10 , in accordance with embodiments disclosedherein, a pair of ADS pulses 1002, 1004 may be delivered in a way thatmanipulates a transient, partial contraction of a diaphragm in a waythat enhances and adds to the duration of one of a caudal phase or acranial phase of the contraction. For example, it is possible to extendthe duration of a cranial phase 1014 of a transient, partial contractionof the diaphragm for a brief time through delivery of the second ADSpulse 1004 soon after the delivery of the first ADS pulse 1002, withoutthe extended cranial phase overlapping with the delivery of a next ADSpulse 1016 that is triggered by a next cardiac event. A delivery of anADS pulse 1004 for purpose of extending a particular phase ofcontraction is feasible because the refractory period of the diaphragmis short, e.g., between 1 msec. and 4 msec., and nearly independent ofheart rate as the diaphragm tone is driven by respiratory needs. Inother words, even in cases of increased heart rate, there is sufficienttime during a current cardiac cycle 1018 to extend one or both of acranial phase 1014 of a partial contraction or a caudal phase of apartial contraction, before the next cardiac cycle 1020 initiates andtriggers a next ADS pulse 1016.

Further on this embodiment, and with continued reference to FIG. 10 , anappropriately timed and spaced apart pair of ADS pulses including afirst ADS pulse 1002 and a second ADS pulse 1004 may shift the balanceof contraction phases to one of predominantly caudal or predominantlycranial to impact intrathoracic pressure and cardiovascular flow. Tothis end, a portion 202 or part of the diaphragm 204 may be stimulatedas it is moving in either of the caudal phase or the cranial phase of acontraction. By stimulating the portion 202 of the diaphragm 204 priorto that portion completing its transient contraction, the morphology ofthe mechanical response of the portion can be altered in a way to shiftthe balance of the phases of the transient contraction between one thatis predominantly caudal, i.e., the portion 202 of the diaphragm 204moves in the caudal direction for a period of time greater than the timethe part moves in the cranial direction, and predominantly cranial,i.e., the portion 202 of the diaphragm 204 moves in the cranialdirection for a period of time greater than the time the part moves inthe caudal direction.

In one embodiment, a primary function and benefit of second ADS pulse1004 is to shorten the first cranial phase initiated by the first ADSpulse 1002 as it might come too early during a cardiac cycle 1018. Thesecond ADS pulse 1004 cuts that first cranial phase short and creates asecond cranial phase later in the cardiac cycle 1018 when there ishemodynamic benefit achieved by increasing the pressure on theheart/vessels. An illustration of a shift in diaphragm accelerationresulting from the delivery of a pair of appropriately timed consecutiveADS pulses 1002, 1004 is shown in FIG. 10 . The first ADS pulse 1002results in a typical caudal-followed-by-cranial transient, partialcontraction 1006 or twitch of the diaphragm having a caudal phase 1008followed by the beginning of a first cranial phase 1010. During thefirst cranial phase 1010 of the transient, partial contraction, a secondADS pulse 1004 is delivered. For example, the timing of delivery of thesecond ADS pulse 1004 may be based on the typical time for a diaphragmto complete a transient, partial contraction. This contraction time istypically between 60 to 180 msec., with the caudal phase taking abouthalf the total time and the cranial phase taking half the total time.Accordingly, an appropriately timed second ADS pulse 1004 for purposesof extending a cranial phase 1014 may be delivered somewhere between50-75 msec. after the delivery of the first ADS pulse 1002.

Delivery of the second ADS pulse 1004 at this time overlaps with theeffect of the first ADS pulse 1002 and induces a sharp change, e.g.,reduction, in the acceleration of the diaphragm in the cranialdirection. This change in acceleration manifests graphically in FIG. 10as a narrow-width first cranial phase 1010 having a short, near-verticaldrop downward to the baseline 1019. Subsequent to this reduction inacceleration, the second ADS pulse 1004 induces an increase inacceleration of the diaphragm in the cranial direction, followed by areduction in the acceleration of the diaphragm in the cranial direction.These changes in acceleration manifests graphically in FIG. 10 as asecond cranial portion 1012. The second cranial portion 1012, togetherwith the first cranial portion 1010 produce an overall diaphragmaticcontraction that is predominately cranial. In other words, the balanceof the overall diaphragm movement is shifted to the cranial phase. Thisis beneficial because movement of the diaphragm in the cranial directionresults in an increase in intrathoracic pressure, which in turnincreases the pressure on the heart and vessels in a way that itaugments cardiac output if timed correctly to the beginning of systole.

FIG. 11 is a flowchart of a method of affecting pressure in anintrathoracic cavity of a patient through delivery of paired ADS pulses.The method may be performed by the IMD of FIG. 7 or a similar apparatusor system. For example, the method may be performed by an apparatushaving one or more electrodes 722, 724 configured for placement on ornear a diaphragm and a controller 702 coupled to the one or moreelectrodes. The controller 702 is configured, for example, thoughexecutable program instructions stored in a memory, to perform themethod described below with reference to FIG. 11 .

At block 1102, and with additional reference to FIG. 10 , a firststimulation pulse 1002 is delivered to a diaphragm of the patient. Thefirst stimulation pulse 1002 is configured to induce a transient,partial contraction 1006 of the diaphragm comprising a caudal phase 1008corresponding to a time during which a portion of the diaphragm ismoving in a caudal direction, followed by a cranial phase 1010corresponding to a time during which the portion of the diaphragm ismoving in the cranial direction.

Delivery of the first stimulation pulse 1002 to the diaphragm may betriggered by a cardiac event. To this end, and with additional referenceto FIG. 8A, an occurrence of a cardiac event 816, e.g., an R wave, isdetected by the IMD 700, and the first stimulation pulse 1002 is outputby the IMD at or near the end of a first offset period 814 from thedetected cardiac event. The occurrence of a cardiac event 816 may bedetected based on signals sensed by the one or more electrodes 722, 724configured for placement on or near the diaphragm, or by one or moreelectrodes 712, 714 placed on or near a heart, or by a motion sensor 716placed on or near a heart.

At block 1104, a second stimulation pulse is delivered to the diaphragmwhile the diaphragm is still in motion from the first stimulation pulse1002. The second stimulation pulse may be configured to extend aduration of one of the caudal phase 1008 and the cranial phase 1014 ofthe transient, partial contraction of the diaphragm. To this end, thestimulation parameters, e.g., pulse amplitude, pulse width, etc., thatdefine the second stimulation pulse may be the same as the stimulationparameters that define the first stimulation pulse 1002. Alternatively,the stimulation parameters that define the second stimulation pulse maybe different. For example, it may be beneficial for the secondstimulation pulse to have a higher stimulation energy to solicit a moreforceful response of the diaphragm through the second stimulus, andthereby increasing the hemodynamic effect the resulting extended caudalmovement or cranial movement could have.

Delivery of the second stimulation pulse to the diaphragm may betriggered by or timed to various different events. For example, withreference to FIG. 10 , which illustrates the effect of a secondstimulation pulse 1004 that extends the duration of a cranial phase1014, the second stimulation pulse 1004 may be output by the IMD 700 ator near the end of a second offset period 1022 that may be timedrelative to the delivery of the first stimulation pulse 1002. Forexample, the IMD 700 may be programmed to output the second stimulationpulse 1004 between 20 msec. and 300 msec. after delivery of the firststimulation pulse 1002. In another configuration, the second offsetperiod may be relative to an occurrence of a cardiac event. This cardiacevent may be the same cardiac event that triggered the delivery of thefirst stimulation pulse 1002.

In another configuration, the IMD 700 is configured to determine thesecond offset period 1022 by detecting a pair of closely associatedcardiac events in a cardiac cycle. For example, a pair of closelyassociated cardiac events may include a first cardiac event, e.g., Qpoint 822 of a QRS complex, associated with a beginning of a systolicphase of a cardiac cycle and a second cardiac event 824, e.g., S1 heartsound, that follows the first cardiac event and is also associated withthe systolic phase. A number of pairs of closely associated cardiacevents may be detected over a number of cardiac cycles. The IMD 700 isconfigured to calculate the second offset period 1022 based on timingdifferences, or the intervals between the first cardiac event 822 andthe second cardiac event 824 of each pair. The second offset period 1022is calculated based on the intervals. The second offset period 1022 maybe the average of the determined intervals, or it may be the averageinterval adjusted by a fixed factor, e.g., x %. For example, the secondoffset period 1022 may be set to 90% of the average interval.

In another configuration, delivery of the second stimulation pulse 1004may be triggered based on diaphragm motion. To this end, the motionphase, e.g., caudal phase or cranial phase, of the diaphragm may bedetermined based on signals from a motion sensor 720. For example, withreference to FIGS. 7 and 10 , the diaphragm motion analysis module 738of the IMD 700 controller 702 may be configured to monitor the motionsignal of the diaphragm to detect a fiducial point of the cranial phase1010 resulting from the first stimulation pulse 1002, and output thesecond stimulation pulse 1004 upon such detection. The triggeringfiducial point of the cranial phase may be at or near a peak or aninflection point 1024 of the cranial phase 1010.

In the case of extending the caudal phase (which is not shown in FIG. 10), the IMD 700 controller 702 may be configured to monitor the motionsignal of the diaphragm to detect a fiducial point of the caudal phase1008 resulting from the first stimulation pulse 1002, and output thesecond stimulation pulse upon such detection. This will prolong thecaudal phase and thereby increase the duration of negative intrathoracicpressure and less pressure on the heart/vessels, thereby extending aperiod of better filling of the heart.

In another configuration, multiple second stimulation pulses may bedelivered to extend each of the caudal phase and the cranial phase. Inthis configuration, a “first” second stimulation pulse may be deliveredat an appropriate time after the first stimulation pulse 1002 and duringthe caudal phase. For example, the “first” second stimulation pulse maybe delivered at the peak of the caudal phase 1008 shown in FIG. 10 tothereby extend the caudal phase. At the end of the extended caudalphase, and while the diaphragm is in a cranial phase, a “second” secondstimulation pulse may be delivered at an appropriate time to extend thecranial phase.

Combined Dual-Pulse and Paired-Pulse ADS Therapy

With reference to FIGS. 8B and 10 , in an accordance with anotherembodiment, an ADS therapy may combine the dual-pulse ADS therapy andthe paired-pulse ADS therapy. To this end, a first ADS pulse 802 of adual-pulse ADS therapy is delivered during late diastole, followed bythe delivery of a second ADS pulse 804 of the dual-pulse ADS therapyduring early systole. This second ADS pulse 804 also functions as afirst ADS pulse 1002 of a paired-pulse ADS therapy. With reference toFIG. 10 , the first ADS pulse 1002 (corresponding to the second ADSpulse 804) and a second ADS pulse 1004 are delivered during earlysystole.

Returning to FIG. 8B, the first ADS pulse 802 delivered during latediastole produces a corresponding transient, partial contraction 808 ofthe diaphragm having a caudal phase 830 and a cranial phase 832, each ofnormal duration. Jumping to FIG. 10 , the pair of ADS pulses 1002, 1004delivered during early systole produces a corresponding transient,partial contraction 1006 of the diaphragm having a caudal phase 1008 andan extended cranial phase 1010, 1012.

Thus, in the combined dual-pulse and paired-pulse ADS therapy, three ADSpulses are delivered per cardiac cycle. The first ADS pulse produces anormal transient, partial contraction of the diaphragm during thediastolic phase, while the second and third ADS pulses produce anextended transient, partial contraction of the diaphragm during thesystolic phase having an enhanced cranial phase.

Multiple-Pulse ADS Therapy

With reference to FIG. 12B, in accordance with embodiment disclosedherein, multiple, e.g., two or more, ADS pulses are delivered during acardiac cycle based on heart rate. Prior to describing themultiple-pulse ADS therapy, reference is made to FIG. 12A for purposesof describing the theory behind multiple pulse ADS therapy. In FIG. 12A,a diaphragmatic acceleration signal 1202 includes a number of spacedapart pairs of transient, partial diaphragmatic contractions 1204superimposed on top of an underlying respiratory signal 1206. Each pairof transient, partial diaphragmatic contractions 1204 results from theabove described dual-pulse ADS therapy, by which two ADS pulses 1208 aredelivered so that a pair of contractions 1204 occur during each of thecardiac cycles 1210 shown in a ECG signal 1212.

The diaphragmatic acceleration signal 1202 of FIG. 12A was capturedthrough an animal model with a heart rate of 120 bpm, which correspondsto an RR interval of 500 msec. The duration or pulse width 1214 of eachcontraction 1204 is largely independent of heart rate. For example, thepulse width 1214 of a contraction 1204 does not shorten as a result ofincreased heart rate. In other words, diaphragmatic tone is driven byrespiratory but not cardiac tone. Accordingly, the number of ADS pulses1208 that may be delivered during a cardiac cycle 1210 in a way thatresults in no overlapping of contractions 1204 depends on the actualheart rate/RR interval. For example, with an RR interval of 500 msec.and a pulse width 1214 of about 100 msec., the maximum number ofpotentially effective transient, partial contractions 1204 would be 5.At 60 bpm (RR 1000 msec.) the maximum number of potentially effectivetransient, partial contractions 1204 doubles to 10.

With reference to FIG. 12B, a diaphragmatic acceleration signal 1222includes a continuous stream of transient, partial contractions 1224 ofthe diaphragm superimposed on top of an underlying respiratory signal1226. Each of the partial contractions 1224 result from a correspondingADS pulse 1228, where ADS pulses are delivered so that nine contractionsoccur during each cardiac cycle 1230. In accordance with multiple-pulseADS therapy, the mechanical modulation, i.e., the transient, partialcontraction or twitching, of the diaphragm is in a constant, sinus wavelike motion. Accordingly, the portion of the diaphragm that iscontracting is continuously going back and forth through the caudalphase and cranial phases but is still well synchronized to the cardiaccycle 1230.

The number of transient, partial contractions per cardiac cycle 1230,otherwise referred to as the “twitch frequency,” depends on the heartrate. In one implementation, the number of ADS pulses 1228 and resultingtwitches or transient, partial contractions 1224 is selected so thatonly full twitch cycles are present. A full twitch cycle means that theportion of the diaphragm that is contracting goes through a completecaudal phase and a complete cranial phase before a next ADS pulse 1228is delivered. To this end, the number of ADS pulses 1228 is an integernumber that is based on the heart rate range or RR interval. Forexample, for an RR interval in the range of 1000 msec. to 1099 msec.,and assuming a twitch duration of 100 msec., the number of ADS pulses1228 delivered per cardiac cycle 1230 is ten.

FIG. 13 is a flowchart of a method of affecting pressure in anintrathoracic cavity of a patient through delivery of multiple ADSpulses per cardiac cycle. The method may be performed by the IMD 700 ofFIG. 7 or a similar apparatus or system. For example, the method may beperformed by an apparatus having one or more electrodes 722, 724configured for placement on or near a diaphragm and a controller 702coupled to the one or more electrodes. The controller 702 is configured,for example, though executable program instructions stored in a memory,to perform the method described below with reference to FIG. 13 . Inthis method, ADS pulses are delivered independent of any detectedcardiac events. In other words, the delivery of multiple pulse ADStherapy is not triggered by or synchronized with a detection of acardiac event.

At block 1302, a heart rate of the patient is determined. To this end,the controller 702 may be configured to detect a number of cardiacevents over a number of corresponding cardiac cycles based on signalssensed by the one or more electrodes 722, 724 configured for placementon or near the diaphragm, or signals sensed by one or more electrodes712, 714 configured for placement on or near the heart, or based onsignals sensed by a motion sensor 716 configured for placement on ornear the diaphragm or on or near a heart.

At block 1304, a duration of a transient, partial contraction of thediaphragm of the patient is determined. The partial contraction of thediaphragm includes a caudal phase corresponding to a time during which aportion of the diaphragm is moving in a caudal direction, followed by acranial phase corresponding to a time during which the portion of thediaphragm is moving in the cranial direction. This duration may bedetermined based on acceleration signals sensed, for example, by amotion sensor 720 of the IMD 700 located on or near the diaphragm. Asdescribed above with reference to FIG. 7 , the motion sensor 720 may bean accelerometer configured to be positioned on or near a diaphragm tosense motion of the diaphragm, and to output electrical signalsrepresentative of such motion to the diaphragm motion/heart soundsanalysis module 738 of the controller 702. Alternatively, the motionsensor may be configured to be positioned in, on, or adjacent to anintrathoracic structure, e.g. heart, pericardium, great artery and vein,within the intrathoracic cavity. In this case, the motion sensor may beassociated with a device configured to be implanted remote from thecontroller 702 and to provide signals sensed by the motion sensor to thecontroller through a wireless communication link.

At block 1306, the plurality of stimulation pulses to be delivered tothe patient during a cardiac cycle is calculated based on the heart rateand the duration of a transient, partial contraction of the diaphragm.To this end, the controller 702 is programmed to calculate the number ofADS pulses to be delivered per cardiac cycle. For example, the numbermay be calculated as follows:N=RR/CPW

where, N=the number of ADS pulses to be delivered per cardiac cycle

-   -   RR=heart rate measured as the interval between consecutive R        waves    -   CPW=the pulse width of a transient, partial contract of the        diaphragm

At block 1308, the plurality of stimulation pulses are delivered to adiaphragm of the patient during a cardiac cycle of the patient. Thespacing between ADS pulses is such that each of the plurality ofstimulation pulses results in a corresponding transient, partialcontraction of the diaphragm.

The delivery of multiple ADS pulses per cardiac cycle may occur on acontinuous basis, or may occur periodically, for a predetermined periodof time. For example, the controller 702 of the IMD 700 may beprogrammed to turn multiple-pulse ADS therapy on once per day for aperiod of multiple hours, e.g., four hours. The controller 702 is alsoconfigured to continuously or periodically redetermine the heart rateand to adjust the number of ADS pulses delivered per cardiac cycleaccordingly.

Electromyography (EMG) Sensing

With reference to FIG. 7 , in accordance with embodiments disclosedherein, EMG sensing and analysis capability may be included in an IMD700. The EMG sensing enables the IMD 700 to assess diaphragmatic healthand/or heart failure decompensation status of the patient and to adjustADS therapy. In addition, the EMG sensing enables the IMD 700 to detectpotential IMD operational issues, e.g., impaired cardiac event sensingand detection, and to adjust IMD setting accordingly.

EMG signals may be collected by the IMD 700 through one or more EMGsensors located on the diaphragm. In one configuration an EMG sensorcorresponds to a pair of electrodes that are placed on or near thediaphragm. These electrodes may be the electrodes 712, 714 of thecardiac event source 706, or the electrodes 722, 724 of the ADS therapydelivery mechanism 100, and are thus configured and located to sensecardiac electrical activity, e.g., ECG signals, as well as EMG activity.Accordingly, the signals sensed by the EMG sensor are described hereinas composite ECG/EMG signals.

The therapy module 740 of an IMD 700 may be modified to include an EMGanalysis module 760 that is configured to analyze composite ECG/EMGsignals to assess diaphragmatic health and/or heart failuredecompensation status. Such analyses may involve a comparison betweencharacteristics, e.g., morphology, frequency content, amplitude, of EMGcontent of the composite ECG/EMG signals collected during ADS therapyand corresponding baseline characteristics collected prior to ADStherapy activation. The collection and comparison may occur periodicallywhile ADS therapy is active, for example, once a day.

FIG. 14A is an example of a baseline composite ECG/EMG signal 1402collected after implant of an IMD 700 in a patient, but prior toactivation of ADS therapy. This baseline composite ECG/EMG signal 1402is an ECG signal 1406 that has an EMG signal superimposed therein. EMGcontent or EMG electrical activity of the baseline composite ECG/EMGsignal 1402 appear, for example, as regions 1408 of rapid oscillationsthat are most notable between the R waves 1410 of the ECG signal 1406.

FIG. 14B is an example of another composite ECG/EMG signal 1404collected after activation of ADS therapy when the patient ishemodynamically decompensated. For example, the patient may havesymptoms of shortness of breath. This composite ECG/EMG signal 1404 isan ECG signal 1412 that has an EMG signal superimposed therein. The EMGcontent of this composite ECG/EMG signal 1404 appear, for example, asregions 1416 of rapid oscillations. These regions 1416 of rapidoscillations have an increased amplitude relative to similar regions1408 of the baseline composite EMG signal 1402, and serve as evidence ofhemodynamic decompensation. The increase in EMG amplitude results fromincreased effort by the diaphragm during full diaphragmatic contraction(inspiration). The increased effort, in turn, is due to an increase inair inflow resistance in the lungs that occurs when heart failurepatients start to decompensate (fluid accumulation in the lungs). Asdescribed later below, with reference to FIG. 18 , these types ofchanges in EMG electrical activity or EMG content may be monitoredovertime to assess patient health, independent of ADS therapy. In otherwords, a baseline composite ECG/EMG signal and subsequent ECG/EMGsignals of a patient may be obtained and compared to determine patienthealth by a monitoring device that does not include an ADS therapymodule, or one by a monitoring device that may include a deactivated ADStherapy module.

As previously mentioned, EMG signals may be used to assess the health ofa patient's diaphragm and phrenic nerve. For example, the state ofhealth of a diaphragm and phrenic nerve may be gleaned from EMG signals,such as those shown in FIGS. 15A, 15B, and 15C, which respectivelyillustrate pure EMG signals 1502, 1504, 1506 without any ECG component.FIG. 15A is an example EMG signal 1502 sensed from a patient with ahealthy diaphragm and phrenic nerve. FIG. 15B is an example EMG signal1504 sensed from a patient with a phrenic nerve exhibiting neuropathy.FIG. 15C is an example EMG signal 1506 sensed from a patient with adiaphragm exhibiting myopathy. Analyses of these signals would involve atime/frequency analysis for to assess morphology/pattern changes and acomparison to the last baseline, i.e. between two IPG device follow-ups.

In accordance with embodiments disclosed herein, an IMD 700 senses andstores recordings of composite ECG/EMG signals 1404 like those shown inFIG. 14B and periodically derives a measure of the EMG content of thecomposite ECG/EMG signal and compares it to a baseline measure that isbased on composite ECG/EMG signal 1402 like that shown in FIG. 14A. Forexample, the IMD 700 may calculate the EMG amplitude daily and compareit to a baseline amplitude. The IMD 700 may calculate a statisticalmeans based on a number of measures collected over a period of time,e.g., number of days, to ensure that a potential change in a measure isstatistically significant, and not just a outlier measure. As anexample, the IMD 700 may calculate a z-score for each individual measureand trend the z-scores.

Once the statistical measure is obtained, the IMD 700 compares themeasure to the baseline measure to determine if a threshold criterion issatisfied that indicates a decrease in diaphragmatic and/or phrenicnerve health and/or heart failure decompensation status. In one example,the threshold may be considered satisfied when the statistical measurerepresents at least a 50% increase over the baseline measure. In anotherexample, the threshold may be considered satisfied after a predeterminednumber or percentage, e.g., 8 out of 10, or 80%, of individualstatistics measures represent an increase over the baseline measure.

Various type of actions may result from a forgoing determination that athreshold criterion is satisfied that indicates a decrease indiaphragmatic and/or phrenic nerve health and/or heart failuredecompensation status. For example, a notification may be provided tothe clinician during an IMD 700 follow-up (typically every 3 to 6months). Alternatively, the IMD may include wireless communicationcapability that enables the IMD 700 to transmit relevant information toa clinician at predefined time intervals, e.g., daily, weekly, etc., orwhen a predefined EMG amplitude threshold has been reached.

As previously mentioned, beyond assessing diaphragmatic health and/orheart failure decompensation status of the patient, EMG signals, or morespecifically, the EMG content of composite ECG/EMG signals, may be usedto adjust ADS therapy. To this end, one or more stimulation parametersof the IMD 700 may be automatically adjusted to improve effectiveness ofthe ADS therapy. For example, the energy of the ADS pulses may beincreased, e.g., pulse amplitude increased, up to a predefined valuewhich still allows the ADS pulses to be imperceptible to the patient.Such a predefined value may be determined post IMD implant throughthreshold/symptoms testing when patient in conscious. In a case ofpatient decompensation, the fluid accumulation could also lead to a wetdiaphragm requiring more stimulation energy for ADS therapy to beeffective. In another example, the offset period or delay period betweendetected cardiac events and ADS pulse delivery may be adjusted toaccount for the effect of heart failure decompensation on cardiacrhythm. To this end, the timing of cardiac events in ECG content incomposite ECG/EMG signals may be analyzed over time, e.g., days, todetermine a new offset period or delay period for ADS therapy.

In some cases, composite ECG/EMG signals may also be used toautomatically turn ADS therapy off. For example, if the EMG noiseamplitude in a signal increases to a level that impairs cardiac eventsensing, e.g., R wave detection, it could impact the consistency andsynchronicity of ADS pulse delivery to the cardiac cycle, hence leadingto an ineffective ADS therapy. To address this issue, in oneconfiguration the IMD 700 may be configured to sense consistency of Rwave sensing, and deactivate ADS therapy for as long as a consistencycriterion is fulfilled. A consistency criterion may include a measure ofvariability of detected R wave timing (ventricular sense events outsideof the refractory period) that exceeds a predetermined physiologicthreshold or other statistical analysis criteria based on the IMD'ssensing/stimulation history. In another configuration, the IMD 700 maybe configured to sense the signal-to-noise ratio (SNR), i.e., R waveamplitude versus EMG amplitude in a composite ECG/EMG signal, anddeactivate ADS therapy for as long as a certain SNR criterion isfulfilled. A SNR criterion may include a measure of SNR that fails toexceed a threshold SNR. For example, the SNR criterion may be set to2:1, thus requiring the R wave amplitude to be at least twice that ofthe EMG amplitude. Otherwise, ADS therapy is deactivated. In eitherconfiguration, deactivation of ADS therapy may be accompanied by anotification to the clinician.

As previously mentioned, composite ECG/EMG signals may also be used todetect potential IMD operational issues. To this end, one or moresensing parameters of the IMD 700 may be adjusted when the EMG noiseamplitude impacts the ability of the IMD to reliably sense occurrencesof relevant cardiac events, e.g., ECG features, such as an R wave,detections of which are relied on to deliver effective ADS therapy. Ifthe IMD 700 detects impaired R wave sensing, i.e. through consistency ofdetected R wave timing (ventricular sense events outside of therefractory period), the IMD may decrease the sensitivity setting for thesensing channel until the sensing returns to the consistency it had atbaseline, prior to the EMG amplitude increase. If the R wave amplitudeis small and the EMG noise drastically increases, it might not bepossible to find a suitable sensitivity setting. In that case, the IMD700 may automatically temporarily suspend the ADS therapy until the EMGnoise is reduced and/or notify the clinician.

With reference to FIGS. 7, 16A, 16B, 16C, the controller 702 of an IMD700 may include a ECG/EMG filter module 762 configured to affect acomposite ECG/EMG signal 1602, 1604, 1606 captured by one or moreelectrodes 712, 714, 722, 724 on or near the diaphragm. In oneconfiguration, the ECG/EMG filter module 762 may be set to capture oneor more different frequency ranges or bands of the ECG component and EMGcomponent of the composite ECG/EMG signals 1602, 1604, 1606 toselectively enable better detection and analysis of one of the EMGcontent or the ECG content.

The composite ECG/EMG signal 1602 of FIG. 16A is captured when thefilter is set to a wideband state (1-180 Hz), and includes EMG noise1608 superimposed on a far-field ECG signals 1610. The composite ECG/EMGsignal 1604 of FIG. 16B is captured when the filter is set to a wideband(70-180 Hz) state. This filter state favors EMG content 1612 over ECGcontent 1614 and allows the controller 702 of the IMD 700 to bettersense and assess the EMG signal characteristics including amplitude. Thecomposite ECG/EMG signal 1606 of FIG. 16C is captured when the filter isset to a narrowband (10-50 Hz) state. This filter state favors ECGcontent 1616 over EMG content 1618. This filter state attenuates the EMGcontent and allows the IMD to better sense and assess the ECG content,e.g., R waves.

FIG. 17 is a flowchart of a method of modifying sensing and/orstimulation parameters for an apparatus that affects pressure in anintrathoracic cavity of a patient through delivery of ADS. The methodmay be performed by the IMD 700 of FIG. 7 or a similar apparatus orsystem. For example, the method may be performed by an apparatus havingone or more electrodes 722, 724 configured for placement on or near adiaphragm and a controller 702 coupled to the one or more electrodes.The controller 702 is configured, for example, though executable programinstructions stored in a memory, to perform the method described belowwith reference to FIG. 17 .

In this embodiment, the IMD 700 further includes a ECG/EMG filter module762 that enables a composite ECG/EMG signal received from an inputsensing channel provided by the electrodes 712, 714 to be subjected totwo types of filtering, including a filtering that enables better EMGfeature detection, and a filtering that enables better ECG feature,e.g., R wave, detection. In one implementation, composite ECG/EMGsignals from the sensing channel are directed along two filter pathswithin the ECG/EMG filter module 762, each having a respective filter.The first filter is a narrowband filter configured to attenuate the EMGcontent to thereby emphasize the ECG content for cardiac event sensingdetection (see FIG. 16C, described below). The second filter is awideband filter configured to output a signal that contains both ECGcontent and an EMG content (see FIG. 16B, described below). The latteris used to assess the EMG amplitude through different means, i.e. simpleSNR analysis up to more sophisticated frequency or even wavelet templatematching, as described further below.

Returning to FIG. 17 , at block 1702, ADS therapy in the form of ADSpulses defined by one or more stimulation parameters, is delivered tothe patient over a period of time. To this end, the IMD 700 senses acomposite ECG/EMG signal 1404 through an input sensing channel, such asa channel provided by electrodes 712, 714. The IMD 700 filters thecomposite ECG/EMG signal 1404 to better enable detection of ECGelectrical activity over EMG electrical activity. For example, thecomposite ECG/EMG signal 1404 may be filtered to a narrowband (10-50 Hz)state by a ECG/EMG filter module 762 to produce a filtered compositeECG/EMG signal 1606 like the one shown in FIG. 16C. The IMD 700 thenprocesses the filtered composite ECG/EMG signal 1606 to detect anelectrical cardiac event in the ECG content 1616 present in the signal.For example, the IMD 700 may detect one or more ECG features, e.g., Rwaves 1620. The IMD 700 then outputs one or more ADS pulses responsiveto the detected electrical cardiac event in accordance with one or moreof the ADS therapies described above.

At block 1704, EMG electrical activity produced by one or more skeletalmuscles of the diaphragm is periodically sensed over the period of timein accordance with one or more sensing parameters. The one or moresensing parameters of the IMD, which are initially set and programmed bythe clinician, may include: 1) a sensing sensitivity (measured inmillivolts) which is a reference voltage in a signal comparator tofacilitate the detection of cardiac event, e.g., ECG fiducial points,such as R wave detections, and 2) timing windows that include a)blanking intervals (measured in msec.) which are windows where the IMDis blinded to the ECG signal for the purpose of ECG fiducial detections,and b) refractory periods (measured in msec.) which are windows wherethe IMD senses the ECG signal and detects ECG fiducials, but does notuse those detections for the purpose of delivering ADS pulses to thediaphragm. “Blinded” means that the sensing channel of the IMD is turnedoff. This is necessary after an ADS pulse is delivered to the diaphragmas resulting afterpotential would overdrive the sensing amplifier of theIMD sensing channel during the stimulus. Accordingly, the sensingchannel of the IMD gets “blanked” until the afterpotentials are smallenough to not cause a problem. The duration of the blanking interval istypically determined by the clinician.

Continuing with block 1704, the IMD 700 senses a composite ECG/EMGsignal 1404 through an input sensing channel, such as a channel providedby electrodes 712, 714. The IMD 700 filters the composite ECG/EMG signal1404 to better enable detection of EMG electrical activity over ECGelectrical activity. For example, the composite ECG/EMG signal 1404 maybe filtered to a wideband (70-180 Hz) state by a ECG/EMG filter module762 to produce a filtered composite ECG/EMG signal 1604 like the oneshown in FIG. 16B. The composite ECG/EMG signal 1604 is then processedto detect electrical activity features in the EMG content 1612 of thesignal. For example, the IMD 700 may detect one or more of EMG signalamplitude, EMG signal frequency, or EMG signal morphology.

At block 1706, the IMD 700 determines if the EMG electrical activitysatisfies a criterion relative to baseline EMG electrical activity ofthe patient that is sensed prior to ADS therapy activation. To this end,the IMD 700 may compare a morphology characteristic, e.g., R wave width,of the EMG content in the filtered composite ECG/EMG signal 1604 (seeFIG. 16B) with a baseline of the morphology characteristic. The IMD 700may compare a frequency characteristic, e.g., high frequency content, ofthe EMG content in the filtered composite ECG/EMG signal 1604 (see FIG.16B) with a baseline of the frequency characteristic. The IMD 700 maycompare an amplitude characteristic of the EMG content in the filteredcomposite ECG/EMG signal 1604 (see FIG. 16B) with a baseline of theamplitude characteristic.

At block 1708, at least one of a stimulation parameter and a sensingparameter is adjusted if the criterion is not satisfied. For example, inthe case of a morphology comparison in block 1706, an increase in thewidth of the R wave due to higher EMG signal strength in the compositeECG/EMG signal, e.g., the wideband filtered signal 1604 shown in FIG.16B, relative to a baseline could trigger an adjustment of sensingparameter, e.g., decrease the sensitivity setting (increase in referencevoltage). In the case of a frequency characteristic comparison in block1706, an increase in higher frequency content when looking at aspectrogram of the composite ECG/EMG signal, e.g., the wideband filteredsignal 1604 shown in FIG. 16B, relative to a baseline could trigger anadjustment of sensing parameter, e.g., decrease the sensitivity setting(increase in reference voltage). In the case of an amplitude comparisonin block 1706, an increase in amplitude of the composite ECG/EMG signal,e.g., the wideband filtered signal 1604 shown in FIG. 16B, within a timeperiod in the cardiac cycle, which does not contain any prominent ECGfiducial, i.e. not around the R wave, P wave of T wave, relative to abaseline could trigger an adjustment of sensing parameter, e.g.,decrease the sensitivity setting (increase in reference voltage).

In other examples regarding sensing parameters, the sensing sensitivityof the input sensing channel may be reduced to lower the presence of EMGcontent in a composite ECG/EMG signal to thereby reduce the impact ofthe EMG signal on the ability of the IMD 700 to detect R waves.Regarding stimulation parameters, the stimulation energy of ADS pulsemay be increased or the offset period of the ADS pulse may be adjustedto improve the effectiveness of the therapy. The IMD 700 may suspend thedelivering of ADS therapy while it is adjusting at least one of thestimulation parameters and the sensing parameters.

Stimulation Parameters

The ADS therapy delivered by the IMD is defined by stimulationparameters that include: 1) one or more pulse parameters having a valueor setting selected to define a stimulation pulse that induces atransient, partial contraction of the diaphragm, and 2) a timingparameter that controls the timing of the delivery of one or more ADSpulses. The pulse parameters may include, for example, a pulse waveformtype, a pulse amplitude, a pulse duration, and a pulse polarity. Thetiming parameter may include one or more offset periods or delay periodsthat defines a time between a detected cardiac event and a delivery ofan electrical stimulation pulse.

With respect to the pulse parameters, as previously described, atransient, partial contraction of the diaphragm typically entails a veryshort (only a few tens of milliseconds) pulse-like, biphasic(singular-caudal followed by singular-cranial) asymptomatic motion ofthe diaphragm. The IMD 700, including in particular the therapy module740, is configured to generate stimulation pulses that result in veryshort, biphasic asymptomatic motion of the diaphragm. To this end, thetherapy module 740 may be configured to select a setting of square,sinusoidal, triangular, or sawtooth for the pulse waveform type, and toselect a setting of positive or negative for the pulse polarity. Thetherapy module 740 may be further configured to select a value for thepulse amplitude that is between 0.0 volts and 7.5 volts, and to select avalue for the pulse duration that is between 0.0 milliseconds and 5milliseconds.

Regarding the timing parameter, the therapy module 740 may be configuredto determine one or more offset periods or delay periods. As previouslydescribed, the delay period may be based on the time between successivedetected cardiac events. For example, the EGM analysis module 732 of thecardiac signal module 728 may be configured to detect ventricularevents, e.g., R waves, and to output such detections to the therapymodule 740. The cardiac-event analysis module 742 may process thedetected ventricular events to determine a statistical measure of timebetween a number of pairs of successive ventricular events. Thecardiac-event analysis module 742 may then determine a delay periodbased on the statistical measure and an offset relative to thestatistical measure, and control the pulse generator 746 to output ADSpulses based on the determined offset period or delay period.

Initial selection of pulse parameter settings and values and the timingparameter by the therapy module 740 may be performed by a physicianthrough an external device, e.g., a programmer. In this case, theexternal device provides selection commands to the therapy module 740through a wireless communication link, and the therapy module selectsthe pulse parameters and timing parameter in accordance with thecommands. Alternatively, selection of pulse parameter settings andvalues and the timing parameter by the therapy module 740 may beautomated.

Sensing Parameters

As previously mentioned, the sensing parameters of the IMD 700 mayinclude: 1) a sensing sensitivity, which is a reference voltage in asignal comparator to facilitate the detection of cardiac event, e.g.,ECG fiducial points, such as R wave detections, and 2) timing windowsthat include a) a blanking interval, which is a portion of a cardiaccycle during which the IMD is blinded to the ECG signal for the purposeof ECG fiducial detections, and b) a refractory period which is aportion of a cardiac cycle during which the IMD senses the ECG signaland analyzes the ECG signal to detect ECG fiducials, but does not usethose detections for the purpose of delivering ADS pulses to thediaphragm.

Regarding the sensitivity parameter, this parameter is used to set thevalue of a reference voltage, e.g., a threshold voltage, that iscompared with the varying amplitude of the EMG content within compositeECG/EMG signals. A higher sensitivity voltage means that the IMD 700 isless sensitive to the ECG content within the composite ECG/EMG signalsfor the purpose of detecting cardiac events, e.g., fiducial pointscorresponding to R waves. If the reference voltage is too high andlarger than the ECG content, then no fiducial points, e.g., R waves, canbe detected. This condition is referred to as undersensing. If thereference voltage is much lower than the SNR, then inadequate detectionof fiducial points, e.g., R-waves, can occur. This condition is referredto as oversensing. When the EMG content within a composite ECG/EMGsignal becomes larger due to diaphragmatic stress (represented by noisein the EMG signal, such as shown in FIG. 14B), the SNR measured by theIMD 700 goes down relative to a baseline SNR, and the likelihood ofoversensing goes up. As a counter measure, upon detection of an SNRindicative of oversensing the IMD 700 may automatically decrease thesensing sensitivity setting by increasing the reference voltage.Similarly, the IMD 700 may monitor the consistency of R wave detectionsover time to detect oversensing and adjust the sensing parameter bydecreasing sensing sensitivity.

In one configuration, the IMD 700 may include a sensitivity voltageparameter having a value or setting, e.g., between 0.1 millivolts and 10millivolts, selected to set a reference voltage to compare with ECGcontent in a filtered ECG/EMG composite signal and to facilitate thedetection of cardiac events, e.g., R waves or other fiducials, in theECG signal as a timing reference for the delivery of ADS pulses. Forexample, the sensitivity voltage of the previously described narrowbandfilter of the ECG/EMG filter module 762 may be adjusted to produce acomposite ECG/EMG signal 1606 with ECG content having well-pronounced Rwaves 1620 for cardiac event sensing detection purposes (see FIG. 16C).Or, in other words, the reference voltage may be increased until the SNRincreases to an appropriate level, i.e., a level that does not fulfillthe SNR criterion described above, or the R wave consistency measureincreases to an appropriate level, i.e., a level that does not fulfillthe consistency criterion described above.

Regarding the timing window parameters, these parameters, e.g., blankingintervals and refractory periods, generally correspond to time periodsin the cardiac cycle in which therapy relevant ECG fiducial points areunlikely to be present and/or where artifacts like signal noise and ADSpulse afterpotentials could lead to false detections. The blankingintervals and refractory periods are set by the clinician to increasethe specificity of cardiac event detections, e.g., the fiducial pointdetections, such as R waves, with which ADS pulse delivery issynchronized. The blanking intervals and refractory periods allow theIMD 700 to only use certain time periods in the cardiac cycle which havea high likelihood to contain the ECG fiducial points meant to bedetected for purposes of delivering ADS therapy. During these certaintime periods, the signal analysis performed by the IMD 700 includessignal analysis for detecting the presence of cardiac events, e.g., Rwaves, or other ECG fiducials, classifying each such detected cardiacevent as a valid cardiac event or a non-valid event, e.g., noise (eventsdetected during absolute refractory times), and delivering ADS pulsesaccordingly. In essence, the blanking interval and refractory perioddrive the action taken by the IMD state machine, i.e. if and when asignal threshold crossing (sensing event) leads to a diaphragm stimulus.The signal analyzed by the IMD 700 for purposes of detecting cardiacevents may correspond to the narrowband filtered composite ECG/EMGsignal 1606 shown in FIG. 16C.

Blanking intervals, which are intervals during which the IMD is blindedto the composite ECG/EMG signal for the purpose of ECG fiducialdetections, are applied in time periods with high likelihood ofcontaining artifacts. For example, a blanking interval may correspond toa period of time, e.g., 20 msec., after delivery of an ADS pulse to thediaphragm during which corresponding afterpotentials may impact the ECGcontent of sensed composite ECG/EMG signals and to lead to detections ofnon-valid cardiac events. These blanking intervals are not changed dueto the detection of EMG noise.

Refractory periods allow the detection of ECG fiducials, but suchdetections are not used to trigger delivery of ADS pulses. The signalanalysis performed by the IMD during refractory periods includes signalanalysis for detecting the presence of cardiac events or conditions forwhich ADS therapy delivery should not occur, e.g., certain heart rates,including elevated heart rates at or near an upper tracking rateprogrammed in the IMD 700. The signal analyzed by the IMD 700 forpurposes of detecting cardiac events may correspond to the narrowbandfiltered composite ECG/EMG signal 1606 shown in FIG. 16C.

A refractory period may correspond to a period of time, e.g., 400 msec.,after the detection of an R wave or the delivery of cardiac pacingpulse, in the case of a heart that is subjected to cardiac pacingtherapy. In the case of sensed composite ECG/EMG signals havingincreased EMG noise, which would lead to detection of non-valid cardiacevent, e.g., false R wave detections, and thereby to falsely timed ADSpulse delivery, the IMD 700 may adjust the refractory period byincreasing its length. For example, the IMD 700 may be configured tosense the SNR, i.e., R wave amplitude versus EMG amplitude, and increasethe refractory period when a certain SNR criterion is fulfilled. Aspreviously described, a SNR criterion may include a measure of SNR thatfails to exceed a threshold SNR. For example, the SNR criterion may beset to 2:1, thus requiring the R wave amplitude to be at least twicethat of the EMG amplitude. Similarly, the IMD 700 may monitor theconsistency of R wave detections over time to detect oversensing andadjust the refractory period by increasing it. In either case, therefractory period may be increased up to a point where the IMD 700 doesnot deliver any ADS pulses as the prolonged refractory period suppressany cardiac event detections that trigger ADS pulse delivery, therebyeffectively disabling ADS therapy.

Monitoring Device

In another embodiment, an IMD for monitoring patient health may beinclude components and modules for sensing and analyzing the ECG contentand EMG content of composite ECG/EMG signals similar to those describedwith respect to FIG. 7 . This IMD may be configured to only monitorcomposite ECG/EMG signals to determine diaphragm/patient health. Inother words, the IMD does not include an ADS therapy module.Alternatively, this IMD may have ADS therapy capabilities that areturned off. In either case, in addition to its monitoring capabilities,this IMD may be configured to store and/or transmit the datacorresponding to signal sensing and analysis to a clinician for laterinterpretation by the clinician.

FIG. 18 is a flowchart of a method of monitoring patient health. Themethod may be performed by an IMD similar to the IMD 700 of FIG. 7 , butwithout ADS therapy capability. For example, the method may be performedby an apparatus having one or more electrodes 712, 714 configured forplacement on or near a diaphragm and a controller 702 coupled to the oneor more electrodes. The controller 702 may include the cardiac signalmodule 728, the pressure signal module 730, the EMG analysis module 760,the memory subsystem 748, the communication subsystem 750, the powersupply 752, and the clock supply 754. The controller 702 is configured,for example, though executable program instructions stored in a memory,to perform the method described below with reference to FIG. 18 .

At block 1802, EMG electrical activity produced by one or more skeletalmuscles of the diaphragm is periodically sensed over the period of time.To this end, the IMD 700 senses a composite ECG/EMG signal 1404 throughan input sensing channel, such as a channel provided by electrodes 712,714. The IMD 700 filters the composite ECG/EMG signal 1404 to betterenable detection of EMG electrical activity over ECG electricalactivity. For example, the composite ECG/EMG signal 1404 may be filteredto a wideband (70-180 Hz) state by a ECG/EMG filter module 762 toproduce a filtered composite ECG/EMG signal 1604 like the one shown inFIG. 16B. The composite ECG/EMG signal 1604 is then processed to detectEMG signal features in the EMG content 1612 present in the signal. Forexample, the IMD 700 may detect one or more of EMG signal amplitude, EMGsignal frequency, or EMG signal morphology.

At block 1804, the IMD 700 determines if the EMG electrical activitysatisfies a criterion relative to baseline EMG electrical activity ofthe patient. To this end, the IMD 700 may compare a morphologycharacteristic, e.g., R wave width, of the EMG content in the filteredcomposite ECG/EMG signal 1604 (see FIG. 16B) with a baseline of themorphology characteristic. The IMD 700 may compare a frequencycharacteristic, e.g., high frequency content, of the EMG content in thefiltered composite ECG/EMG signal 1604 (see FIG. 16B) with a baseline ofthe frequency characteristic. The IMD 700 may compare an amplitudecharacteristic of the EMG content in the filtered composite ECG/EMGsignal 1604 (see FIG. 16B) with a baseline of the amplitudecharacteristic.

The criterion corresponds to a deviation indicative of a change inpatient health. For example, in the case of a morphology comparison, athreshold increase in the width of the R wave present in a widebandfiltered composite ECG/EMG signal (such as shown in FIG. 16B) relativeto a baseline R wave width may be considered to correspond to a declinein patient health. In the case of a frequency characteristic, athreshold increase in higher frequency content when looking at aspectrogram of a wideband filtered composite ECG/EMG signal (such asshown in FIG. 16B) relative to the same frequency content in a baselinemay be considered to correspond to a decline in patient health. In thecase of an amplitude comparison, a threshold increase in amplitude ofthe EMG content 1612 present in a wideband filtered composite ECG/EMGsignal (such as shown in FIG. 16B) within a time period in the cardiaccycle, relative to the same amplitude within the same time period of acardiac cycle of a baseline may be considered to correspond to a declinein patient health. A threshold increase may be a predetermine amount orpercentage increase in the relative measure.

The various aspects of this disclosure are provided to enable one ofordinary skill in the art to practice the present invention. Variousmodifications to exemplary embodiments presented throughout thisdisclosure will be readily apparent to those skilled in the art, and theconcepts disclosed herein may be extended to other magnetic storagedevices. Thus, the claims are not intended to be limited to the variousaspects of this disclosure, but are to be accorded the full scopeconsistent with the language of the claims. All structural andfunctional equivalents to the various components of the exemplaryembodiments described throughout this disclosure that are known or latercome to be known to those of ordinary skill in the art are expresslyincorporated herein by reference and are intended to be encompassed bythe claims. Moreover, nothing disclosed herein is intended to bededicated to the public regardless of whether such disclosure isexplicitly recited in the claims. No claim element is to be construedunder the provisions of 35 U.S.C. § 112, sixth paragraph, unless theelement is expressly recited using the phrase “means for” or, in thecase of a method claim, the element is recited using the phrase “stepfor.”

What is claimed is:
 1. An apparatus for affecting pressure in anintrathoracic cavity of a patient, the apparatus comprising: one or moreelectrodes configured for placement on or near a diaphragm; a controllercoupled to the one or more electrodes, and configured to: deliver asingle diastolic stimulation pulse to the diaphragm of the patientduring a diastolic phase of a cardiac cycle of the patient by beingfurther configured to: detect an occurrence of a first cardiac event,and deliver the single diastolic stimulation pulse at or near the end ofa diastolic offset period from the detected occurrence of a firstcardiac event that places the delivery of the single diastolicstimulation pulse at a latter part of diastole of the cardiac cycle; anddeliver a single systolic stimulation pulse to the diaphragm during asystolic phase of the cardiac cycle by being further configured to:detect an occurrence of a second cardiac event, and deliver the singlesystolic stimulation pulse at or near the end of a systolic offsetperiod from the detected occurrence of a second cardiac event thatplaces the delivery of the single systolic stimulation pulse at an earlypart of systole of the cardiac cycle, wherein each of the singlediastolic stimulation pulse and the single systolic stimulation pulseresults in an asymptomatic, transient, partial contraction of thediaphragm.
 2. The apparatus of claim 1, wherein the controller isfurther configured to determine the diastolic offset period by beingfurther configured to: detect, over a plurality of cardiac cycles, atime of occurrence of: a) the first cardiac event, b) one of an onset ofan atrial event and an offset of a first ventricular event, and c) anonset of a second ventricular event that follows the onset of the atrialevent or the onset of the first ventricular event; and process therespective times of occurrences to calculate a period of time from thefirst cardiac events to a time between: a) either of an onset of anatrial event or an offset of a first ventricular event, and b) an onsetof a second ventricular event that follows the onset of the atrial eventand the onset of the first ventricular event, wherein the period of timecorresponds to the diastolic offset period.
 3. The apparatus of claim 2,wherein: each of the onset of an atrial event and the offset of a firstventricular event correspond to a detected P wave, and the onset of asecond ventricular event corresponds to a detected Q point in a QRScomplex, or a detected S1 heart sound.
 4. The apparatus of claim 1,wherein the controller is further configured to determine the systolicoffset period by being further configured to: detect, over a pluralityof cardiac cycles, a time of occurrence of: a) the second cardiac event,b) one of an onset of electrical systole and an onset of mechanicalsystole, and c) one of an offset of electrical systole and an offset ofmechanical systole; and process the respective times of occurrences tocalculate a period of time from the second cardiac events to a timebetween: a) either of an onset of electrical systole or an onset ofmechanical systole, and b) either of an offset of electrical systole oran offset of mechanical systole, wherein the period of time correspondsto the systolic offset period.
 5. The apparatus of claim 4, wherein: anonset of electrical systole corresponds to a detected Q point in a QRScomplex, and an onset of mechanical systole corresponds to a detected S1hear sound, and an offset of electrical systole corresponds to adetected T wave, and an offset of mechanical systole corresponds to adetected S2 heart sound.
 6. The apparatus of claim 1, wherein the firstcardiac event and the second cardiac event are a same cardiac event typein consecutive cardiac cycles, the same cardiac event type correspondingto one of an electrical event and a mechanical event.
 7. The apparatusof claim 1, wherein the first cardiac event and the second cardiac eventare different cardiac events in a same cardiac cycle, each of thedifferent cardiac events corresponding to one of an electrical event anda mechanical event.
 8. The apparatus of claim 1, wherein the controlleris configured to detect at least one of the occurrence of a firstcardiac event and the occurrence of a second cardiac event based onsignals sensed by the one or more electrodes configured for placement onor near the diaphragm.
 9. The apparatus of claim 1, further comprisingone or more electrodes configured for placement on or near a heart,wherein the controller is configured to detect at least one of theoccurrence of a first cardiac event and the occurrence of a secondcardiac event based on signals sensed by one or more electrodesconfigured for placement on or near the heart.
 10. The apparatus ofclaim 1, further comprising a motion sensor configured for placement onor near the diaphragm or on or near a heart, wherein the controller isconfigured to detect at least one of the occurrence of a first cardiacevent and the occurrence of a second cardiac event based on signalssensed by the motion sensor.
 11. A method of affecting pressure in anintrathoracic cavity of a patient, the method comprising: delivering asingle diastolic stimulation pulse to a diaphragm of the patient duringa diastolic phase of a cardiac cycle of the patient, wherein deliveringthe single diastolic stimulation pulse comprises: detecting anoccurrence of a first cardiac event, and delivering the single diastolicstimulation pulse at or near the end of a diastolic offset period fromthe detected occurrence of a first cardiac event that places thedelivery of the single diastolic stimulation pulse at a latter part ofdiastole of the cardiac cycle; and delivering a single systolicstimulation pulse to the diaphragm during a systolic phase of thecardiac cycle, wherein delivering the single systolic stimulation pulsecomprises: detecting an occurrence of a second cardiac event; anddelivering the single systolic stimulation pulse at or near the end of asystolic offset period from the detected occurrence of a second cardiacevent that places the delivery of the single systolic stimulation pulseat an early part of systole of the cardiac cycle, wherein each of thesingle diastolic stimulation pulse and the single systolic stimulationpulse results in an asymptomatic, transient, partial contraction of thediaphragm.
 12. The method of claim 11, further comprising determiningthe diastolic offset period by: detecting, over a plurality of cardiaccycles, a time of occurrence of: a) the first cardiac event, b) one ofan onset of an atrial event and an offset of a first ventricular event,and c) an onset of a second ventricular event that follows the onset ofthe atrial event or the onset of the first ventricular event; andprocessing the respective times of occurrences to calculate a period oftime from the first cardiac events to a time between: a) either of anonset of an atrial event or an offset of a first ventricular event, andb) an onset of a second ventricular event that follows the onset of theatrial event and the onset of the first ventricular event, wherein theperiod of time corresponds to the diastolic offset period.
 13. Themethod of claim 12, wherein: each of the onset of an atrial event andthe offset of a first ventricular event correspond to a detected P wave,and the onset of a second ventricular event corresponds to a detected Qpoint in a QRS complex, or a detected S1 heart sound.
 14. The method ofclaim 11, further comprising determining the systolic offset period by:detecting, over a plurality of cardiac cycles, a time of occurrence of:a) the second cardiac event, b) one of an onset of electrical systole,and an onset of mechanical systole, and c) one of an offset ofelectrical systole, and an offset of mechanical systole; and processingthe respective times of occurrences to calculate a period of time fromthe second cardiac events to a time between: a) either of an onset ofelectrical systole or an onset of mechanical systole, and b) either ofan offset of electrical systole or an offset of mechanical systole,wherein the period of time corresponds to the systolic offset period.15. The method of claim 14, wherein: an onset of electrical systolecorresponds to a detected Q point in a QRS complex, and an onset ofmechanical systole corresponds to a detected S1 hear sound, and anoffset of electrical systole corresponds to a detected T wave, and anoffset of mechanical systole corresponds to a detected S2 heart sound.16. The method of claim 11, wherein the first cardiac event and thesecond cardiac event are a same cardiac event type in consecutivecardiac cycles, the same cardiac event type corresponding to one of anelectrical event and a mechanical event.
 17. The method of claim 11,wherein the first cardiac event and the second cardiac event aredifferent cardiac events in a same cardiac cycle, each of the differentcardiac events corresponding to one of an electrical event and amechanical event.